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WO2012060308A1 - Médicament pour la prévention et le traitement de dysfonctionnement rénal - Google Patents

Médicament pour la prévention et le traitement de dysfonctionnement rénal Download PDF

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Publication number
WO2012060308A1
WO2012060308A1 PCT/JP2011/075022 JP2011075022W WO2012060308A1 WO 2012060308 A1 WO2012060308 A1 WO 2012060308A1 JP 2011075022 W JP2011075022 W JP 2011075022W WO 2012060308 A1 WO2012060308 A1 WO 2012060308A1
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WO
WIPO (PCT)
Prior art keywords
group
substituted
pyridyl
unsubstituted
cyano
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/JP2011/075022
Other languages
English (en)
Japanese (ja)
Inventor
龍祐 坂本
大哉 橋本
真彦 伏見
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sanwa Kagaku Kenkyusho Co Ltd
Fuji Yakuhin Co Ltd
Original Assignee
Sanwa Kagaku Kenkyusho Co Ltd
Fuji Yakuhin Co Ltd
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 Sanwa Kagaku Kenkyusho Co Ltd, Fuji Yakuhin Co Ltd filed Critical Sanwa Kagaku Kenkyusho Co Ltd
Priority to JP2012541838A priority Critical patent/JP5862897B2/ja
Publication of WO2012060308A1 publication Critical patent/WO2012060308A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • C07D401/14—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 three or more hetero rings
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/04—Drugs for disorders of the urinary system for urolithiasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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

Definitions

  • the present invention relates to a medicine used for prevention or treatment of renal dysfunction.
  • the kidney is responsible for excretion of water, electrolytes, and metabolites (including foreign substances) in the blood, and maintaining the homeostasis of the body environment through regulation of body fluid volume, blood osmotic pressure, and acid-base balance It is a special organ. There are about 1 million nephrons in one kidney. In nephron, blood is filtered in the glomeruli, useful plasma components and water are reabsorbed from the filtrate in the tubules, and secretion and excretion in the tubules are performed. ing. This decline in kidney function reduces the homeostasis of the body environment and, if severe, results in death.
  • GFR Filtration volume
  • Chronic kidney disease including chronic renal failure among kidney diseases, has a certain period of time that suggests some kind of kidney damage or has a GFR below a certain value (60ml / min / 1.73m 2 in Japan ). (3 months in Japan).
  • pharmacotherapy is one of the main complications of suppressing the progression of chronic kidney disease
  • Antihypertensive drugs are sometimes used for the purpose of reducing the risk of cardiovascular diseases.
  • the cure is difficult unless it is early or mild chronic kidney disease.
  • Non-Patent Document 1 a xanthine oxidase inhibitor
  • allopurinol and febuxostat which is another xanthine oxidase inhibitor, have an action of protecting renal function during ischemia reperfusion
  • Patent Document 2 In allopurinol, renal diseases of chronic kidney disease patients It has been reported that there is an effect of delaying the progress (Non-Patent Document 2).
  • Allopurinol and its main active metabolite, oxypurinol are purine-like compounds, but administration of allopurinol inhibits xanthine oxidase and increases xanthine, and oxypurinol is excreted in the urine and is neutral.
  • Xanthine and oxypurinol are less soluble than uric acid in urine, and kidney stones and urinary calculi containing these purines are also known to occur, and oxypurinol may be the main component of these stones. It has been reported (for example, Non-Patent Documents 4 and 5). Therefore, administration of a purine-like compound xanthine oxidase inhibitor such as allopurinol may cause purine-derived calculus formation and adversely affect renal function.
  • the 1,2,4-triazole compound which is the compound of the present invention is a compound described in Patent Document 2, but the preventive or therapeutic effect of the compound on renal dysfunction is not known.
  • An object of the present invention is to provide a medicament for use in the prevention or treatment of renal dysfunction with few side effects.
  • R 2 represents an unsubstituted pyridyl group or a substituted pyridyl group having a cyano group, a lower alkyl group, a halogen, a lower alkoxy group or a lower alkylthio group as a substituent.
  • R 1 may have a halogen, cyano group, or phenyl group as a substituent, an unsubstituted or substituted pyridyl group, or a pyridine N-oxide group corresponding to these pyridyl groups, or a cyano group as a substituent
  • a substituted phenyl group having a nitro group, or the cyano group or nitro group a substituted or unsubstituted lower alkoxy group, an N-lower alkyl-substituted piperazino group, a lower alkylthio group, a phenylthio group, Or the substituted phenyl group which has a lower alkylamino group is shown.
  • R 1 is not a phenyl group substituted with only one cyano group or a phenyl group substituted with only one nitro group.
  • R 2 is an unsubstituted pyridyl group or a lower alkyl-substituted pyridyl group
  • R 1 is an unsubstituted pyridyl group, a lower alkyl-substituted pyridyl group, or a pyridine N-oxide group corresponding to these pyridyl groups. is not.
  • R 3 represents hydrogen or a pivaloyloxy-substituted lower alkyl group, each of which is bonded to one nitrogen of the 1,2,4-triazole ring represented by the general formula (1)].
  • 2,4-triazole compound or a pharmaceutically acceptable hydrate or solvate thereof or a salt thereof as an active ingredient used for the prevention or treatment of renal dysfunction.
  • R 2 is an unsubstituted pyridyl group, or a substituted pyridyl group having a cyano group, a lower alkyl group having 1 to 3 carbon atoms, or a halogen as a substituent; 1 may have a halogen or cyano group as a substituent, an unsubstituted or substituted pyridyl group, R 3 is a hydrogen atom, a medicament according to ⁇ 1>.
  • R 2 is an unsubstituted pyridyl group, or a substituted pyridyl group having a lower alkyl group having 1 to 3 carbon atoms or a halogen as a substituent, and R 1 is a substituent.
  • R 1 is a substituent.
  • ⁇ 1> which is a substituted pyridyl group having a cyano group as R 3 is a hydrogen atom.
  • ⁇ 5> The medicament according to any one of ⁇ 1> to ⁇ 4>, wherein the renal dysfunction is renal failure or chronic kidney disease.
  • ⁇ 6> The medicament according to any one of ⁇ 1> to ⁇ 4>, wherein the renal dysfunction is a disease accompanied by a decrease in glomerular filtration rate.
  • the present invention provides a medicament for use in the prevention or treatment of renal dysfunction.
  • the compound which becomes an active ingredient of this invention is a compound which has a xanthine oxidase inhibitory effect, since it is not a purine analog, there is no fear that the kidney stone and urinary tract stone derived from purine will arise.
  • the medicament used for the prevention or treatment of renal dysfunction contains a compound represented by the following general formula (1) as an active ingredient.
  • the said compound is a compound of international publication number WO03 / 064410, and a compound synthesis
  • R 2 represents an unsubstituted pyridyl group or a substituted pyridyl group having a cyano group, a lower alkyl group, a halogen, a lower alkoxy group or a lower alkylthio group as a substituent.
  • R 1 may have a halogen, a cyano group, or a phenyl group as a substituent, an unsubstituted or substituted pyridyl group, a pyridine N-oxide group corresponding to the pyridyl group, or a cyano group as a substituent
  • a substituted phenyl group having a nitro group, or the cyano group or nitro group a substituted or unsubstituted lower alkoxy group, an N-lower alkyl substituted piperazino group, a lower alkylthio group, a phenylthio group, Or the substituted phenyl group which has a lower alkylamino group is shown.
  • R 1 is not a phenyl group substituted with only one cyano group or a phenyl group substituted with only one nitro group.
  • R 2 is an unsubstituted pyridyl group or a lower alkyl-substituted pyridyl group
  • R 1 is an unsubstituted pyridyl group, a lower alkyl-substituted pyridyl group, or a pyridine N-oxide group corresponding to these pyridyl groups. is not.
  • R 3 represents hydrogen or a pivaloyloxy-substituted lower alkyl group, each of which is bonded to one nitrogen of the 1,2,4-triazole ring represented by the general formula (1)]. , 2,4-triazole compounds, or pharmaceutically acceptable hydrates or solvates thereof, or salts thereof.
  • the halogen in the general formula (1) includes fluorine, chlorine, bromine and iodine, and the lower alkyl group is a linear or branched alkyl group having 1 to 6 carbon atoms as the lower alkoxy group.
  • a linear or branched alkoxy group having 1 to 6 carbon atoms a lower alkylthio group is a linear or branched alkylthio group having 1 to 6 carbon atoms
  • a lower alkylamino group is a carbon number 1 To 6 linear or branched alkylamino groups.
  • the N-lower alkyl-substituted piperazino group include an N-substituted piperazino group having a linear or branched alkyl group having 1 to 6 carbon atoms as a substituent.
  • R 2 is an unsubstituted pyridyl group, or a substituted pyridyl group having a cyano group, a lower alkyl group having 1 to 3 carbon atoms, or a halogen as a substituent.
  • R 1 is an unsubstituted or substituted pyridyl group optionally having a halogen or a cyano group as a substituent, and a compound in which R 3 is a hydrogen atom is preferable.
  • R 2 is an unsubstituted pyridyl group, or a substituted pyridyl group having a lower alkyl group having 1 to 3 carbon atoms or halogen as a substituent
  • R 1 is a substituted pyridyl group having a cyano group as a substituent.
  • Particularly preferred are compounds in which R 3 is a hydrogen atom.
  • a C1-C3 lower alkyl group a methyl group or an ethyl group is preferable.
  • the halogen chlorine is preferable.
  • the compound represented by the above general formula is used as a salt, it is not particularly limited as long as it is a pharmaceutically acceptable salt.
  • a pharmaceutically acceptable salt for example, hydrochloride, sulfate, nitrate, phosphate, tartrate, succinate, citric acid
  • Addition salt of inorganic or organic acid such as salt, maleate, fumarate, acetate, lactate, sodium salt, potassium salt, calcium salt, magnesium salt, ammonium salt, ethylenediamine salt, meglumine salt, dieta It can be used as an alkali salt with an inorganic or organic salt such as a nuramine salt or a tris salt.
  • a compound having xanthine oxidase inhibitory action serves as a preventive or therapeutic agent for renal dysfunction.
  • a group of compounds is described in WO92 / 9279, WO2010 / 030988, WO98 / 18765, and JP2000-1431.
  • the inventors have come to recognize that it is a preventive or therapeutic agent for renal dysfunction.
  • renal dysfunction includes various renal diseases related to decreased or impaired renal function.
  • kidney disease is identified as a kidney disease associated with a decrease in GFR and includes chronic kidney disease. More specifically, various glomerular diseases (acute nephritis syndrome, rapid progressive nephritis syndrome, recurrent (recurrent) / continuous hematuria, chronic nephritis syndrome, nephrotic syndrome, hereditary nephropathy (nephropathy), diffuse thread Glomerulonephritis, dense deposit disease, etc.), renal tubulointerstitial disease, renal failure, kidney stones / urinary tract stones, etc.
  • glomerular diseases acute nephritis syndrome, rapid progressive nephritis syndrome, recurrent (recurrent) / continuous hematuria, chronic nephritis syndrome, nephrotic syndrome, hereditary nephropathy (nephropathy), diffuse thread Glomerulonephritis, dense deposit disease, etc.
  • glomerular disease for example, primary glomerular disease (microscopic disease) Variant, focal glomerulosclerosis, membranous nephropathy, mesangial proliferative glomerulonephritis (IgA nephropathy, non-IgA nephropathy), membranous proliferative glomerulonephritis, diffuse sclerosing glomerulonephritis, etc.) Renal diseases based on systematic diseases include collagen disease kidney (scleroderma kidney, lupus nephritis, etc.), diabetic nephropathy, renal amyloidosis, purpura nephritis, renal gout, hereditary renal disease (inheritance) Nephritis, Alport syndrome, Fabry disease, etc.) It can Shimesuru.
  • primary glomerular disease microscopic disease
  • focal glomerulosclerosis membranous nephropathy
  • the medicament of the present invention can be used for prevention or treatment of primary and secondary renal diseases including glomerular lesions in transplanted kidneys including these renal diseases.
  • GFR can be used as an index of the effect of prevention or treatment of these renal dysfunctions, and the effect can be confirmed as maintenance and / or improvement (increase) of GFR.
  • GFR As GFR, (1). Clearance of a renal function diagnostic substance (inulin and the like can be exemplified as a renal functional diagnostic substance, but is not limited to inulin), (2). Clearance of biological materials (creatinine and the like can be exemplified as biological materials, but are not limited to creatinine) and / or (3). Although it is possible to use a numerical value obtained by measuring the concentration of a biological substance in blood (serum or plasma may be used) (such as creatinine as a biological substance, but not limited to creatinine), The GFR measurement method is not limited to (1), (2), and (3).
  • the administration form of the medicament of the present invention is not particularly limited, and examples thereof include oral preparations, injection preparations, and transdermal absorption preparations. It can also be administered alone or in combination with other drugs.
  • tablets, coated tablets, granules, fine granules, powders, capsules, etc. can be prepared by conventional methods, and sugar, gelatin, and other substances that can be used for pharmaceuticals If it is of a shape, it can be appropriately coated if necessary.
  • additives such as pharmaceutically acceptable excipients, binders, disintegrants, lubricants, colorants, and corrigents can be used in appropriate combinations as necessary.
  • an injection it can be in a dosage form for intravenous, subcutaneous, intramuscular, intradermal, or other sites where it can be administered as an injection.
  • the storage shape may be either solid or liquid. If necessary, additives such as pharmaceutically acceptable solubilizers, pH adjusters, buffers, suspending agents, stabilizers, tonicity agents, preservatives, etc. are used in appropriate combinations. be able to.
  • the dosage of the medicament of the present invention is the degree of symptoms, the patient's age, sex, body weight, sensitivity difference, administration route, administration method, administration timing, administration interval, nature of pharmaceutical preparation, type of active ingredient, type of concomitant drug
  • the dose may vary depending on the dosage, combined use with other agents, etc., and is not particularly limited, but is usually about 0.1 to 5000 mg, preferably about 1 to 1000 mg, more preferably about 10 to 500 mg per day for an adult. It can be administered orally or parenterally in several or several times.
  • the present invention will be further described with reference to examples, but the present invention is not limited thereto.
  • the medicament of the present invention can also be referred to as the pharmaceutical composition of the present invention.
  • Examples 1-3 Production of uncoated tablets containing 5- (2-cyano-4-pyridyl) -3- (4-pyridyl) -1,2,4-triazole 5- (2-cyano-4-pyridyl)- After mixing 3- (4-pyridyl) -1,2,4-triazole, lactose hydrate, crystalline cellulose, croscarmellose calcium and hydroxypropyl cellulose in the component ratios shown in Table 1, the appropriate amount of water was added. In addition, the mixture was granulated with stirring, and then dried using a fluidized bed granulation coating apparatus at an intake temperature of 80 ° C., an intake air flow rate of 20 m 3 / min, and an exhaust temperature of 40 ° C.
  • the dried product was sized with a 30-mesh sieve, and then magnesium stearate was added and mixed in the composition ratio of the formulation example to obtain granules for tableting. This was tableted so as to have the mass shown in the prescription example per tablet to obtain an uncoated tablet.
  • Test Example 1 eGFR improving action in humans (8 weeks administration) The transition of eGFR (estimated GFR) in humans was examined by the test method described below. Test method: 186 subjects were administered 5- (2-cyano-4-pyridyl) -3- (4-pyridyl) -1,2,4-triazole for a total of 8 weeks according to the dosage and schedule shown in Table 2. The eGFR was calculated from the serum creatinine concentration.
  • Test result 1 Table 3 shows the amount of change in eGFR after 2 weeks, 4 weeks and 8 weeks from the start of administration. As is clear from Table 3, the compound of the present invention has a significant eGFR improvement (eGFR increase) action, and is considered to have an inhibitory effect on a decrease in renal function and an effect to restore renal function. .
  • eGFR increase eGFR improvement
  • Test Example 2 eGFR improving action in humans (30 weeks administration) The transition of eGFR (estimated GFR) in humans was examined by the test method described below. Test method: 5- (2-cyano-4-pyridyl) -3- (4-pyridyl) -1,2,4-triazole, 20 mg once a day for 2 weeks (initial I) 2 times a day 40 mg once a day for 4 weeks (initial II) from 2 weeks to 6 weeks after the start of administration, and 60 mg once a week for 24 weeks (maintenance period) from 6 to 30 weeks after the start of administration Is orally administered twice a day.
  • 5- (2-cyano-4-pyridyl) -3- (4-pyridyl) -1,2,4-triazole 20 mg once a day for 2 weeks (initial I) 2 times a day 40 mg once a day for 4 weeks (initial II) from 2 weeks to 6 weeks after the start of administration, and 60 mg once a week for 24 weeks (main
  • the serum uric acid level at 14 weeks after the start of administration (after 8 weeks of the maintenance phase) is 6.0 mg / dL or more
  • 80 mg is orally administered twice a day.
  • administration was started with a schedule of administration to 240 subjects for a total of 30 weeks, and eGFR was calculated from the serum creatinine concentration.
  • Test result 2 Table 4 shows eGFR and the amount of change before and after the start of administration. As is apparent from Table 4, the compound of the present invention has a significant eGFR improvement (eGFR increase) action, and is considered to have an inhibitory effect on a decrease in renal function and an effect to restore renal function. .
  • eGFR increase eGFR improvement

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un médicament pour la prévention et le traitement de dysfonctionnement rénal. Selon l'invention, un médicament pour la prévention et le traitement de dysfonctionnement rénal comprend, comme principes actifs, un composé 1,2,4-triazole, un hydrate ou un solvate pharmaceutiquement acceptable de celui-ci, ou un sel pharmaceutiquement acceptable de celui-ci, représenté par la formule générale (1). [Dans la formule, R2 représente un groupe pyridyle non substitué ou un groupe pyridyle substitué présentant un groupe cyano, un groupe alkyle inférieur, un halogène, etc. comme groupe substituant. R1 représente groupe pyridyle non substitué ou substitué, etc. qui peut présenter un halogène, un groupe cyano, etc. comme groupe substituant. R3 représente hydrogène, etc., et est lié à un azote d'un cycle 1,2,4-triazole représenté par la formule générale (1).].
PCT/JP2011/075022 2010-11-01 2011-10-31 Médicament pour la prévention et le traitement de dysfonctionnement rénal Ceased WO2012060308A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2012541838A JP5862897B2 (ja) 2010-11-01 2011-10-31 腎機能障害の予防又は治療に用いる医薬

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JP2010-244876 2010-11-01
JP2010244876 2010-11-01

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WO2012060308A1 true WO2012060308A1 (fr) 2012-05-10

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104758263A (zh) * 2015-04-22 2015-07-08 青岛正大海尔制药有限公司 一种托匹司他片及其制备方法
CN105997906A (zh) * 2016-03-16 2016-10-12 江苏悦兴药业有限公司 一种托吡司他片剂及其制备方法
WO2018097294A1 (fr) 2016-11-28 2018-05-31 帝人ファーマ株式会社 Médicament thérapeutique ou médicament prophylactique pour une néphropathie diabétique

Citations (2)

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Publication number Priority date Publication date Assignee Title
WO2003064410A1 (fr) * 2002-01-28 2003-08-07 Fuji Yakuhin Co., Ltd. Nouveau compose 1,2,4-triazole
JP2010509372A (ja) * 2006-11-13 2010-03-25 タケダ・フアーマシユーテイカルズ・ノース・アメリカ・インコーポレイテツド キサンチン酸化還元酵素阻害剤を使用する腎機能保持方法

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JP2665564B2 (ja) * 1989-08-25 1997-10-22 株式会社大塚製薬工場 細胞防護剤

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WO2003064410A1 (fr) * 2002-01-28 2003-08-07 Fuji Yakuhin Co., Ltd. Nouveau compose 1,2,4-triazole
JP2010509372A (ja) * 2006-11-13 2010-03-25 タケダ・フアーマシユーテイカルズ・ノース・アメリカ・インコーポレイテツド キサンチン酸化還元酵素阻害剤を使用する腎機能保持方法

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Title
ASHIZAWA, N. ET AL.: "Strain differences in the responsiveness between Sprague-Dawley and Fisher rats to nephropathy induced by FYX-051, a xanthine oxidoreductase inhibitor", TOXICOLOGY AND APPLIED PHARMACOLOGY, vol. 217, 2006, pages 260 - 265 *
ISEKI, K. ET AL.: "Significance of Hyperuricemia as a Risk Factor for Developing ESRD in a Screened Cohort", AMERICAN JOURNAL OF KIDNEY DISEASES, vol. 44, no. 4, 2004, pages 642 - 650 *
ISEKI, K. ET AL.: "Significance of Hyperuricemia on the Early Detection of Renal Failure in a Cohort of Screened Subjects", HYPERTENS RES, vol. 24, no. 6, 2001, pages 691 - 697 *
OBERMAYR, R.P. ET AL.: "Elevated Uric Acid Increases the Risk for Kidney Disease", JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, vol. 19, 2008, pages 2407 - 2413 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104758263A (zh) * 2015-04-22 2015-07-08 青岛正大海尔制药有限公司 一种托匹司他片及其制备方法
CN105997906A (zh) * 2016-03-16 2016-10-12 江苏悦兴药业有限公司 一种托吡司他片剂及其制备方法
WO2018097294A1 (fr) 2016-11-28 2018-05-31 帝人ファーマ株式会社 Médicament thérapeutique ou médicament prophylactique pour une néphropathie diabétique
KR20190073473A (ko) 2016-11-28 2019-06-26 데이진 화-마 가부시키가이샤 당뇨병성 신증의 치료약 또는 예방약

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JPWO2012060308A1 (ja) 2014-05-12

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