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WO2009087900A1 - Agent pharmaceutique pour la prévention ou le traitement de maladies accompagnées par une hyperperméabilité vasculaire intraoculaire - Google Patents

Agent pharmaceutique pour la prévention ou le traitement de maladies accompagnées par une hyperperméabilité vasculaire intraoculaire Download PDF

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Publication number
WO2009087900A1
WO2009087900A1 PCT/JP2008/073504 JP2008073504W WO2009087900A1 WO 2009087900 A1 WO2009087900 A1 WO 2009087900A1 JP 2008073504 W JP2008073504 W JP 2008073504W WO 2009087900 A1 WO2009087900 A1 WO 2009087900A1
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Prior art keywords
retinopathy
angiotensin
retinal
methyl
propyl
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PCT/JP2008/073504
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English (en)
Japanese (ja)
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Hiroaki Nakamura
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Daiichi Sankyo Company, Limited
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Publication of WO2009087900A1 publication Critical patent/WO2009087900A1/fr

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    • 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • 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

Definitions

  • the present invention relates to a medicament for preventing or treating a disease associated with increased intraocular vascular permeability comprising an angiotensin II receptor antagonist as an active ingredient.
  • Angiotensin II receptor antagonist is used as a therapeutic agent for cardiovascular diseases such as hypertension, heart disease such as cardiac hypertrophy, heart failure, or myocardial infarction, or stroke or nephritis. It is thought to be due to the inhibition of binding of angiotensin II, which has a strong vasoconstrictive action, to the angiotensin II receptor.
  • cardiovascular diseases such as hypertension, heart disease such as cardiac hypertrophy, heart failure, or myocardial infarction, or stroke or nephritis. It is thought to be due to the inhibition of binding of angiotensin II, which has a strong vasoconstrictive action, to the angiotensin II receptor.
  • As an action of olmesartan on intraocular vascular disease improvement of electroretinogram changes in a diabetic animal model (see, for example, Non-Patent Document 1), and suppression of retinal neovascularization in an animal model of proliferative retinopathy ( For example
  • An object of the present invention is to provide a medicament useful for the prevention or treatment of retinal ischemic disease.
  • olmesartan is highly effective in preventing or treating diseases in which intraocular vascular permeability such as diabetic macular edema is enhanced.
  • the present invention has been completed based on the above findings.
  • the present invention (1) A medicament for preventing or treating retinal ischemic disease, comprising an angiotensin II receptor antagonist as an active ingredient, (2) a medicament for the prevention or treatment of retinal ischemic disease associated with increased intraocular vascular permeability, comprising an angiotensin II receptor antagonist as an active ingredient, (3) Retinal ischemic disease with increased intraocular vascular permeability is diabetic retinopathy (simple retinopathy, preproliferative retinopathy, proliferative retinopathy), retinal vein occlusion, retinal artery occlusion, age-related macular degeneration, (2) the pharmaceutical agent according to (2), which is central serous chorioretinopathy, diabetic macular edema, cystoid macular edema, uveitis, or Behcet's disease (4) An angiotensin II receptor antagonist is 4- (1-hydroxy-1-methylethyl) -2-propyl-1- [2 ′-(1H-t)
  • the angiotensin II receptor antagonist is 4- (1-hydroxy-1-methylethyl) -2-propyl-1- [2 ′-(1H-tetrazol-5-yl). ) Biphenyl-4-ylmethyl] imidazole-5-carboxylic acid and a pharmacologically acceptable ester thereof, and a pharmacologically acceptable salt thereof, the above medicament is provided,
  • the angiotensin II receptor antagonist is (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl 4- (1-hydroxy-1-methylethyl) -2-propyl
  • a medicament as described above which is -1- [2 '-(1H-tetrazol-5-yl) biphenyl-4-ylmethyl] imidazol-5-carboxylate.
  • an angiotensin II receptor antagonist for the manufacture of the above medicament preferably 4- (1-hydroxy-1-methylethyl) -2-propyl-1- [2′- (1H-tetrazol-5-yl) biphenyl-4-ylmethyl] imidazol-5-carboxylic acid and pharmacologically acceptable esters thereof, and pharmacologically acceptable salts thereof
  • Angiotensin II receptor antagonist selected from the group consisting of (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl 4- (1-hydroxy-1-methylethyl) -2-propyl-
  • 1- [2 ′-(1H-tetrazol-5-yl) biphenyl-4-ylmethyl] imidazol-5-carboxylate is provided.
  • diseases associated with increased intraocular vascular permeability preferably diabetic retinopathy (simple retinopathy, preproliferative retinopathy, proliferative retinopathy), retinal vein occlusion, retinal artery occlusion, age-related
  • a method for the prevention or treatment of macular degeneration, central serous chorioretinopathy, diabetic macular edema, cystoid macular edema, uveitis, or Behcet's disease comprising an angiotensin II receptor antagonist, preferably 4- (1- Hydroxy-1-methylethyl) -2-propyl-1- [2 '-(1H-tetrazol-5-yl) biphenyl-4-ylmethyl] imidazol-5-carboxylic acid and pharmacologically acceptable
  • An angiotensin II receptor antagonist selected from the group consisting of pharmaceutically acceptable salts thereof, and more preferably (5-methyl-2-oxo-1,3-diox
  • a method comprising the step of administering a prophylactically or therapeutically effective amount of 5-carboxylate to a mammal, including a human.
  • the inventors of the present invention are (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl ⁇ 4- (1-hydroxy-1-methylethyl) -2, which is a kind of angiotensin II receptor antagonist.
  • -Propyl-1- [2 ′-(1H-tetrazol-5-yl) biphenyl-4-ylmethyl] imidazol-5-carboxylate hereinafter referred to as “olmesartan medoxomil”
  • olmesartan medoxomil is intraocular vascular permeability. It has been shown that olmesartan medoxomil has improved the disease associated with increased intraocular vascular permeability, as far as it is known, and is novel in this regard. Has already been used clinically as an antihypertensive drug, and there are almost no safety issues in patients with diseases with increased intraocular vascular permeability. It is a big feature.
  • the medicament of the present invention containing an angiotensin II receptor antagonist as an active ingredient is diabetic retinopathy (simple retinopathy, preproliferative retinopathy, proliferative retinopathy), retinal vein occlusion, retinal artery occlusion, age-related macular degeneration. It is useful for the prevention or treatment of diseases with increased vascular permeability in the eye, such as central serous chorioretinopathy, diabetic macular edema, cystoid macular edema, uveitis, or Behcet's disease.
  • diseases with increased vascular permeability in the eye such as central serous chorioretinopathy, diabetic macular edema, cystoid macular edema, uveitis, or Behcet's disease.
  • N is the air rearing / solvent administration group
  • V is the oxygen load / solvent administration group
  • CS0.3 is the oxygen load / olmesartan medoxomil 0.3 mg / kg administration group
  • CS1 is the olmesartan medoxomil 1 mg / kg administration group
  • CS3 is the olmesartan The medoxomil 3 mg / kg administration group is shown. Data are expressed as mean ⁇ standard error.
  • an angiotensin II receptor antagonist means a substance that can competitively or non-competitively inhibit the binding of angiotensin II to an angiotensin II receptor.
  • the angiotensin II receptor antagonist may be a low molecular weight organic compound, peptide compound, saccharide compound, or a high molecular compound such as a protein, glycoprotein, or polysaccharide compound. Whether or not a certain substance has an angiotensin II receptor antagonistic activity can be easily confirmed by those skilled in the art, for example, according to the method described in US Pat. No. 5,616,599.
  • the term “angiotensin II receptor antagonist” should not be construed as limiting in any way, but in the broadest sense.
  • angiotensin II receptor antagonist that can be suitably used for the medicament of the present invention, for example, 4- (1-hydroxy-1-methylethyl) -2-propyl-1- [2 ′-(1H-tetrazo- Mention may be made of (l-5-yl) biphenyl-4-ylmethyl] imidazole-5-carboxylic acid, pharmaceutically acceptable esters thereof, or pharmaceutically acceptable salts thereof.
  • Metal salt such as earth metal salt, aluminum salt, iron salt, zinc salt, copper salt, nickel salt, cobalt salt; or ammonium salt, t-octylamine salt, dibenzylamine salt, morpholine salt, glucosamine salt, phenylglycine Alkyl ester salt, ethylenediamine salt, N-methylglucamine salt, guanidine salt, diethylamine salt, triethylamine salt, dicyclohexyl Amines such as amine salts, N, N'-dibenzylethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzyl-phenethylamine salt, piperazine salt, tetramethylammonium salt, tris (hydroxymethyl) aminomethane salt Examples thereof include salts, but are not limited thereto. An alkali metal salt can be preferably used, and a sodium salt can be particularly preferably used.
  • a physically acceptable ester means a compound in which the carboxylic acid moiety in the molecule of the compound is esterified.
  • permitted pharmacologically is not specifically limited, Those skilled in the art can select suitably.
  • the ester is preferably one that can be cleaved in vivo by a biological method such as hydrolysis.
  • Examples of the group constituting the ester include methoxymethyl, 1-ethoxyethyl, 1-methyl-1-methoxyethyl, 1- (iso C1-C4 alkoxy C1 such as propoxy) ethyl, 2-methoxyethyl, 2-ethoxyethyl, 1,1-dimethyl-1-methoxymethyl, ethoxymethyl, propoxymethyl, isopropoxymethyl, butoxymethyl or t-butoxymethyl
  • a C1-C4 alkoxy group such as 2-methoxyethoxymethyl; a C1-C4 alkoxy C1-C4 alkyl group; a C6-C10 aryloxy C1-C4 alkyl group such as phenoxymethyl; Halogenated C1-C4 alkoxy such as trichloroethoxymethyl or bis (2-chloroethoxy) methyl C1-C4 alkyl group; C1-C4 alk
  • a pivaloyloxymethyl group, a phthalidyl group or a (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl group can be used, and more preferably (5-methyl A -2-oxo-1,3-dioxolen-4-yl) methyl group can be used.
  • a hydrohalide such as hydrofluoride, hydrochloride, hydrobromide or hydroiodide; nitrate; perchlorate; sulfate; phosphate; methanesulfonate, trifluoro C1-C4 alkane sulfonate which may be substituted with halogen such as methane sulfonate or ethane sulfonate; C1-C4 alkyl which may be substituted with benzene sulfonate, p-toluene sulfonate, etc.
  • halogen such as methane sulfonate or ethane sulfonate
  • C1-C4 alkyl which may be substituted with benzene sulfonate, p-toluene sulfonate, etc.
  • C6-C10 aryl sulfonates C1-C6 fatty acid salts such as acetic acid, malic acid, fumarate, succinate, citrate, tartrate, succinate or maleate; or glycine salt , Lysine salts, arginine salts, ornithine salts, amino acid salts such as glutamate or aspartate, and the like.
  • C1-C6 fatty acid salts such as acetic acid, malic acid, fumarate, succinate, citrate, tartrate, succinate or maleate
  • glycine salt Lysine salts, arginine salts, ornithine salts, amino acid salts such as glutamate or aspartate, and the like.
  • hydrochloride, nitrate, sulfate, or phosphate can be used, and particularly preferably, hydrochloride can be used.
  • angiotensin II receptor antagonist 4- (1-hydroxy-1-methylethyl) -2-propyl-1- [2 ′-(1H-tetrazol-5-yl) biphenyl-4- Ylmethyl] imidazol-5-carboxylic acid or a pharmaceutically acceptable ester thereof can be used, more preferably 4- (1-hydroxy-1-methylethyl) -2-propyl-1- [ A pharmacologically acceptable ester of 2 ′-(1H-tetrazol-5-yl) biphenyl-4-ylmethyl] imidazol-5-carboxylic acid can be used, and even more preferably, 4- (1-Hydroxy-1-methylethyl) -2-propyl-1- [2 ′-(1H-tetrazol-5-yl) biphenyl-4-ylmethyl] imidazol-5-carboxylic acid Acryloyloxy methyl ester, can be used phthalidyl ester, or (5-(2-
  • ester compound When using a physically acceptable ester, the ester compound may have one or more asymmetric carbons, but the pure form of optical isomers or diastereoisomers based on the asymmetric carbons. Stereoisomers such as isomers, or any mixture or racemate of stereoisomers can also be used.
  • angiotensin II receptor antagonist examples include imidazole derivatives (Japanese Patent Laid-Open Nos. 56-71073, 56-71074, 57-98270, No. 58-157768, USP 4,355,040, USP 4,340,598, etc., EP-253310, EP-291969, EP-324377, EP-403158, WO-9001307, JP-A-63-23868, And pyrrole, pyrazole, and triazole derivatives (USP 5,183,899, EP-323841, EP-409332, and JP-A-1-287071), benzimidazole derivatives (USP4, etc.).
  • physiologically acceptable salts of these compounds, hydrates or solvates of compounds in a free form or a salt form, or derivatives such as prodrugs can also be used.
  • the medicament of the present invention can be used for the prevention or treatment of diseases associated with increased intraocular vascular permeability.
  • prevention or treatment includes improvement or cure of a disease, suppression of progression of the disease, prevention of onset, prevention of recurrence, and the like.
  • prevention or treatment should not be construed as limiting in any way, but the term should be interpreted in the broadest sense.
  • Examples of diseases with increased vascular permeability in the eye include diabetic retinopathy (simple retinopathy, preproliferative retinopathy, proliferative retinopathy), retinal vein occlusion, retinal artery occlusion, age-related macular degeneration, centrality Including serous retina choroidopathy, diabetic macular edema, cystoid macular edema, uveitis, or Behcet's disease.
  • diabetic retinopathy simple retinopathy, preproliferative retinopathy, proliferative retinopathy
  • retinal vein occlusion retinal vein occlusion
  • retinal artery occlusion age-related macular degeneration
  • centrality Including serous retina choroidopathy, diabetic macular edema, cystoid macular edema, uveitis, or Behcet's disease.
  • Diabetic retinopathy (simple retinopathy, preproliferative retinopathy, proliferative retinopathy), retinal vein occlusion, retinal artery occlusion, age-related macular degeneration, central serous chorioretinopathy, diabetic macular edema, cystoid macular edema , Uveitis, or Behcet's disease can be used for prevention or treatment of diseases in which vascular permeability is increased in the eye. Since the above-mentioned angiotensin II receptor antagonist is generally an orally administered drug, it is desirable to administer the medicament of the present invention orally.
  • the administration form of the medicament of the present invention is not limited to oral administration, and can be administered parenterally, for example, intravenous administration, rectal administration, transdermal administration, transmucosal administration, ophthalmic administration, etc.
  • unit dosage forms suitable for oral administration include, but are not limited to, powders, granules, tablets, capsules and the like.
  • Pharmaceutical additives can be used.
  • Pharmaceutical additives include, for example, excipients (eg sugar derivatives such as lactose, sucrose, sucrose, mannitol or sorbitol; starch derivatives such as corn starch, potato starch, alpha starch or dextrin; crystalline cellulose and the like Organic derivatives such as gum arabic; gum arabic; dextran; or pullulan; or silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, calcium silicate, or magnesium metasilicate aluminate; calcium hydrogen phosphate Such as phosphates; carbonates such as calcium carbonate; inorganic excipients such as sulfates such as calcium sulfate), lubricants (eg, stearic acid, calcium stearate or magnesium stearate) Metal stearate Talc; waxes such as bees wax or gay wax; boric acid; adipic acid; sulfate such as sodium sulfate; glycol; fumaric acid
  • the dose of the medicament of the present invention can be appropriately selected according to various factors such as administration route, type of active ingredient, patient age, weight, or symptom, purpose of prevention or treatment, etc. Can be administered in the range of about 0.001 to 1,000 mg, preferably 0.1 to 500 mg, more preferably about 5 to 80 mg as the weight of an angiotensin II receptor antagonist per adult day.
  • FITC-dextran molecular weight 4.4 kDa 100 mg / kg was administered to the femoral vein. The chest was opened 10 minutes later, and a blood sample was obtained from the heart. Subsequently, after securing the drainage path by right atrial appendage incision, PBS was perfused with a pressure of 80 mmHg for 2 minutes from the cannula inserted into the left ventricle, and the retina was removed.
  • the wet weight of the retina was measured, homogenized in 0.3 ml of distilled water, and filtered through a centrifugal filter (Millipore Ultrafree-MC; molecular weight 30,000). Meanwhile, plasma was obtained by centrifugation of the blood sample.
  • the amount of pigment in retinal filtrate and plasma was measured with a microplate reader (excitation wavelength: 485 nm, fluorescence wavelength: 535 nm), and the fluorescence of the retinal filtrate of animals not administered with the pigment was subtracted as a blank.
  • Retinal vascular permeability was determined by dividing the retinal pigment concentration by the plasma pigment concentration and then dividing by the retinal wet weight.
  • Formulation Example 1 Capsule After the powder of the above formulation is mixed and passed through a 60 mesh sieve, this powder is put into a 250 mg No. 3 gelatin capsule to form a capsule.
  • Formulation Example 2 Tablet The powder of the said prescription is mixed and tableted by a tableting machine to make one tablet of 200 mg. This tablet can be sugar-coated if necessary.

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Abstract

L'invention porte sur un agent pharmaceutique utile pour la prévention ou le traitement de maladies ischémiques rétiniennes. De façon spécifique, l'invention porte sur un agent pharmaceutique pour la prévention ou le traitement de maladies ayant une hyperperméabilité vasculaire intraoculaire comprenant une rétinopathie diabétique (une rétinopathie d'arrière-fond simple, une rétinopathie préproliférative, une rétinopathie proliférative), une occlusion de veine rétinienne, une occlusion de l'artère rétinienne, une dégénérescence maculaire liée à l'âge, une choroïdopathie séreuse centrale, un œdème maculaire diabétique, des œdèmes maculaires cystoïdes, une uvéite et la maladie de Behcet. L'agent pharmaceutique comprend, en tant que principe actif, un bloqueur du récepteur II de l'angiotensine tel que l'acide 4-(1-hydroxy-1-méthyléthyl)-2-propyl-1-[2'-(1H-tétrasol-5-yl)biphényl-4-ylméthyl]imidazole-5-carboxylique.
PCT/JP2008/073504 2008-01-11 2008-12-25 Agent pharmaceutique pour la prévention ou le traitement de maladies accompagnées par une hyperperméabilité vasculaire intraoculaire WO2009087900A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011028112A1 (fr) * 2009-09-02 2011-03-10 Valletta Health B.V. Acide imidazole-4-carboxylique utilisé pour traiter une maladie associée à des espèces réactives d'oxygène extracellulaires

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001010975A (ja) * 1999-04-28 2001-01-16 Takeda Chem Ind Ltd 単純網膜症・前増殖網膜症の予防・治療・進展抑制剤
WO2004091659A1 (fr) * 2003-04-15 2004-10-28 Sankyo Company, Limited Medicament destine a la prevention ou au traitement des maladies oculaires angiogeniques
JP2006525269A (ja) * 2003-05-02 2006-11-09 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 糖尿病による微小血管疾患の発症または進行を防止するためのアンジオテンシンｉｉ受容体ブロッカー

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001010975A (ja) * 1999-04-28 2001-01-16 Takeda Chem Ind Ltd 単純網膜症・前増殖網膜症の予防・治療・進展抑制剤
WO2004091659A1 (fr) * 2003-04-15 2004-10-28 Sankyo Company, Limited Medicament destine a la prevention ou au traitement des maladies oculaires angiogeniques
JP2006525269A (ja) * 2003-05-02 2006-11-09 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 糖尿病による微小血管疾患の発症または進行を防止するためのアンジオテンシンｉｉ受容体ブロッカー

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
KNUDSEN, S.T. ET AL.: "Effects of losartan on diabetic maculopathy in type 2 diabetic patients: a randomized, double-masked study", JOURNAL OF INTERNAL MEDICINE, vol. 254, no. 2, 2003, pages 147 - 158 *
MORI, F. ET AL.: "Inhibitory effect of losartan, an AT1 angiotensin II receptor antagonist, on increased leucocyte entrapment in retinal microcirculation of diabetic rats", THE BRITISH JOURNAL OF OPHTHALMOLOGY, vol. 86, 2002, pages 1172 - 1174 *
NAGAI, N. ET AL.: "Suppression of diabetes- induced retinal inflammation by blocking the angiotensin II type 1 receptor or its downstream nuclear factor-kappaB pathway", INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, vol. 48, no. 9, 2007, pages 4342 - 4350 *
NAGAI, N. ET AL.: "Suppression of ocular inflammation in endotoxin-induced uveitis by blocking the angiotensin II type 1 receptor", INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, vol. 46, no. 8, 2005, pages 2925 - 2931 *
NAKAMURA, H. ET AL.: "Pharmacological and pharmacokinetic study of olmesartan medoxomil in animal diabetic retinopathy models", EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 512, 2005, pages 239 - 246 *
SJOLIE, A.K. ET AL.: "Prospects for angiotensin receptor blockers in diabetic retinopathy", DIABETES RESEARCH AND CLINICAL PRACTICE, vol. 76S, 2007, pages S31 - S39 *
SUGIYAMA, T. ET AL.: "Angiotensin II receptor blocker inhibits abnormal accumulation of advanced glycation end products and retinal damage in a rat model of type 2 diabetes", EXPERIMENTAL EYE RESEARCH, vol. 85, no. 3, 2007, pages 406 - 412 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011028112A1 (fr) * 2009-09-02 2011-03-10 Valletta Health B.V. Acide imidazole-4-carboxylique utilisé pour traiter une maladie associée à des espèces réactives d'oxygène extracellulaires

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