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WO2011141419A1 - Association de l'inhibiteur de la xanthine oxydase fébuxostat et de metformine et son utilisation - Google Patents

Association de l'inhibiteur de la xanthine oxydase fébuxostat et de metformine et son utilisation Download PDF

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Publication number
WO2011141419A1
WO2011141419A1 PCT/EP2011/057412 EP2011057412W WO2011141419A1 WO 2011141419 A1 WO2011141419 A1 WO 2011141419A1 EP 2011057412 W EP2011057412 W EP 2011057412W WO 2011141419 A1 WO2011141419 A1 WO 2011141419A1
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WIPO (PCT)
Prior art keywords
metformin
febuxostat
association
pharmaceutically acceptable
xanthine oxidase
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PCT/EP2011/057412
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English (en)
Inventor
Francesco Melani
Sandro Giuliani
Carlo Alberto Maggi
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Menarini International Operations Luxembourg S.A.
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Publication of WO2011141419A1 publication Critical patent/WO2011141419A1/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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to the association of active principles, i.e. of a xanthine oxidase inhibitor with a biguanide derivative, preferably metformin, pharmaceutical compositions comprising said active principles, for use in a human or veterinary therapeutic treatment, and methods for the preparation thereof.
  • active principles i.e. of a xanthine oxidase inhibitor with a biguanide derivative, preferably metformin
  • pharmaceutical compositions comprising said active principles, for use in a human or veterinary therapeutic treatment, and methods for the preparation thereof.
  • Such associations and such compositions proved particularly effective in the treatment of hyperglycemia, alone or in association with hyperuricemia or to other disorders in the clinical context of the metabolic syndrome.
  • Gout is an invalidating chronic disease characterized by hyperuricemia and deposition of monosodium urate crystals in various tissues, mainly at the joint level and in the kidney.
  • Hyperuricemia and gout are frequently associated to other cardiovascular risk factors such as hypertension, hypercholesterolemia and other elements that are part of the metabolic syndrome, like obesity, fasting hyperglycemia, low HDL levels and high triglyceride levels.
  • a xanthine oxidase inhibitor well-known in the literature is allopurinol. More recently, other xanthine oxidase inhibitors have appeared on the market; among them, febuxostat is of particular relevance.
  • Febuxostat is a powerful non-purine selective inhibitor of xanthine oxidase which in clinical studies has been shown to reduce hyperuricemia more effectively than allopurinol.
  • Febuxostat is a thiazole derivative having formula (I), belonging to the class of xanthine oxidase inhibitors, and was originally described in EP513379.
  • EP1020454 it is also described a polymorphic form of febuxostat and a process for obtaining it.
  • references are also found to the potential use of febuxostat in other pathologies.
  • WO2004060489 it is described the use of xanthine oxidase inhibitors for increasing cardiac contractility in CHF (Chronic Heart Failure) patients.
  • febuxostat is used to reduce the QT interval in patients in which such interval is prolonged, and in the pathologies associated thereto.
  • WO2008064015 the use of xanthine oxidase, among which febuxostat, is indicated to preserve renal function.
  • xanthine oxidase inhibitors among which febuxostat, preferably for the treatment of prehypertension characterized by systolic pressure between 120 and 139 mmHg and diastolic pressure between 80 and 89 mmHg; here, xanthine oxidase inhibitors seem to be indicated also in the treatment of more marked hypertensions, though results obtained do not seem to be equal to those of already known anti-hypertensive agents.
  • Hyperglycemia is successfully treated with several drugs belonging to different therapeutic classes. Among them, Metformin, a biguanide derivative which has been used in type 2 diabetes therapy for nearly 50 years, must be considered of particular relevance.
  • Metformin reduces glycemia by decreasing hepatic production of glucose and enhancing insulin action at the level of the muscles and fat. Immediate-release formulations are generally administered once or twice per day, whereas the prolonged- release formulations are administered once per day.
  • Butturini U . et al. in Clinica Terapeutica (1976), 77 (6), 529-541 , has shown that, in subjects with primary hyperuricemia, treatment with allopurinol and metformin can gradually improve hydrocarbon utilization, as well as lipid metabolism.
  • the present invention is based on the surprising discovery made by the Inventors that the association of a xanthine oxidase inhibitor, in particular febuxostat, or pharmaceutically acceptable salts thereof or polymorphic forms thereof, in combination with a biguanide derivative, preferably metformin or pharmaceutically acceptable salts thereof, exhibits a synergistic therapeutic effect in the treatment of hyperglycemia.
  • a xanthine oxidase inhibitor in particular febuxostat, or pharmaceutically acceptable salts thereof or polymorphic forms thereof
  • a biguanide derivative preferably metformin or pharmaceutically acceptable salts thereof
  • a first object of the present invention is an association of the active principles: a) xanthine oxidase inhibitor, febuxostat or pharmaceutically acceptable salts thereof or polymorphic forms thereof; and
  • a second object of the present invention is a pharmaceutical composition comprising, as active principle, a mixture of:
  • xanthine oxidase inhibitor febuxostat, or pharmaceutically acceptable salts thereof or polymorphic forms thereof;
  • one or more pharmaceutically acceptable excipients and/or additives and/or diluents for use in a human or veterinary therapeutic treatment.
  • Another object of the present invention is a method for the preparation of the composition according to the present description, wherein the active mixture
  • the invention entails the advantage of a greater anti-hyperglycemic activity compared to that observed using the sole metformin or the sole xanthine oxidase inhibitor. Moreover, a further advantage is given by the possibility of obtaining significant effects in the treatment of hyperglycemia with a reduced amount of metformin with respect to the monotherapy treatment.
  • the present invention relates to an association of the active principles:
  • association in the present description it is meant an association of the active principles, both in the form of a physical mixture constituted by said active principles in a single dosage unit and in the form of dosage units physically separated for each active principle, but intended for a concomitant administration. In both cases, association must ensure a synergy of the therapeutic effects obtained from the individual active principles with respect to the effect obtained in monotherapy.
  • the non-purine xanthine oxidase inhibitor of said association is preferably febuxostat, a thiazole derivative having formula (I), or pharmaceutically acceptable salts thereof or polymorphic forms thereof.
  • salts of xanthine oxidase inhibitors, and i n particular of febuxostat include but are not limited to cations of alkali metals and of alkaline earth metals, such as lithium, sodium, potassium, calcium, magnesium or aluminium salts, or non-toxic derivatives with quaternary ammonium and cations of a m i n es s u ch a s a m m on i u m , tetra m eth yl a m m o n i u m, tetraethylammonium, methylammonium, dimethylammonium, trimethylammonium, or derive from the addition of organic amines such as ethylendiamine, ethanolamine, diethanolamine, piperazine, tromethamine, lysine, arginine and the like.
  • Polymorphic forms of febuxostat include, but are not limited to the forms described in European Patent EP1020454.
  • Febuxostat its salts or polymorphic forms thereof could be obtained or prepared according to methods described in the known art, like e.g. in EP513379.
  • the second active principle of the association is a biguanide derivative, i.e. metformin.
  • Pharmaceutically acceptable salts of metformin, having a basic function in the molecule include but are not limited to those formally deriving from treatment with inorgan ic or organ ic acids selected from: hydrochloric, hydrobromic, sulfuric, phosphoric, carbonic acids, or organic acids, such as acetic, benzenesulfonic (besylate), methanesulfonic, maleic, malonic, succinic, aspartic, glutamic acid.
  • the pharmaceutically acceptable salt is metformin chlorhydrate.
  • the biguanide derivative, metformin or pharmaceutically acceptable salt thereof is associated to the xanthine oxidase inhibitor, febuxostat, or pharmaceutically acceptable salts thereof or polymorphic forms thereof, in a weight ratio of metformin/febuxostat comprised between 0.4 and 150, or between 2 and 40.
  • febuxostat in an amount comprised between 10-200 mg, or better between 25-100 mg, in association with an amount of metformin comprised between 100-1500 mg, e.g. between 250-100 mg.
  • association envisages a physical mixture of two compounds, as active principles, having the one an acid function and the other one a basic function, also the forming of an internal salt between the two is possible, in proportion to the respective amounts present in the mixture.
  • a further embodiment of the present invention relates to pharmaceutical compositions comprising, as active principle, a mixture of:
  • xanthine oxidase inhibitor febuxostat, or pharmaceutically acceptable salts thereof or polymorphic forms thereof;
  • one or more pharmaceutically acceptable excipients and/or additives and/or diluents for use in a human or veterinary therapeutic treatment.
  • compositions according to the present invention may be formulated in a variety of ways depending on the selected administration route.
  • the pharmaceutical composition is suitable for oral administration of solid forms and may include forms such as capsules, tablets, pills, powders and granules.
  • these solid forms the two active principles, xanthine oxidase inhibitor and metformin, ca n be m i xed wi th o n e o r m o re pharmaceutically acceptable inert excipients.
  • excipients may be selected among those commonly known in the state of the art and include, but are not limited to: a) carriers, such as sodium citrate and calcium phosphate, b) fillers, such as starch, lactose, microcrystalline cellulose, sucrose, glucose, mannitol and colloidal silica, c) moistening agents, such as glycerol, d ) disintegrating agents, such as alginates, calcium carbonate, starches, derivatives of starch, of cellulose and polyvinylpyrrolidone, silicates and sodium carbonate, e) binders, such as carboxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, polymeric derivatives of cellulose, starch derivatives, f) retarding agents, such as paraffin, cellulose polymers, fatty acid esters, g) absorption accelerators, such as quaternary ammonium compounds, h ) wetting agents and surfactants, such as cetyl alcohol and
  • the excipients include but are not limited to compounds of the type: lactose, high molecular weight polyethylene glycol, and the like.
  • Solid-dosage forms such as tablets, capsules, pills and granules, may be coated with enteric, gastric coatings, or coatings of other type well-known in the state of the art. They may contain matting agents and may be of the type such as to allow the release of active ingredients only or preferably in a certain section of the intestine, optionally in a delayed manner. Substances capable of allowing such a delayed use include, but are not limited to polymers and waxes.
  • Liquid forms suitable for oral administration are emulsions, solutions, prepared or extemporary suspensions, syrups and elixirs.
  • Excipients suitable for the formulations according to the present invention in liquid forms for oral use include but are not limited to diluents commonly used in the art, such as water or other solvents, solubilizing and emulsifying agents selected from ethyl alcohol, polyalcohols, propylene glycol, glycerol, polyethylene glycol and sorbitan esters. These formulations can also contain sweeteners and aromas selected from those well-known in the state of the art.
  • compositions suitable for pharmaceutically acceptable parenteral injections may comprise sterile aqueous solutions, sterile dispersions, suspensions or emulsions or powders for a reconstitution in injectable solutions or dispersions; examples of excipients suitable therefor include, but are not limited to aqueous or non-aqueous carriers, diluents, solvents or vehicles selected from: water, ethanol, polyoils (propylene or polyethylene glycol, glycerol, and the like), polyalcohols, isopropyl alcohol, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1.3-butylene glycol, dimethylformamide, vegetable oils (in particular of olive, cotton, peanut, corn, wheat germ, olive, castor, sesame), organic esters such as ethyl oleate or the like.
  • excipients suitable therefor include, but are not limited to aqueous or non-aqueous carriers,
  • compositions may also contain preservatives of antibacterial or antifungal type, selected, yet not exclusively, from: paraben, chlorbutanol, phenol, sorbic acid and the like. It may also be useful to include an isotonic agent, e.g., a sugar, sodium chloride or the like. Moreover, pharmaceutical forms with a delayed absorption may be obtained with agents such as, for instance, yet not exclusively, aluminium monostearate and gelatin.
  • the suspensions may contain suspending agents such as, for instance, yet not exclusively, ethoxylated isostearic alcohols, polyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminium hydroxide, bentonite, alginates and cellulose derivatives in general or the like.
  • suspending agents such as, for instance, yet not exclusively, ethoxylated isostearic alcohols, polyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminium hydroxide, bentonite, alginates and cellulose derivatives in general or the like.
  • the right fluidity can be maintained with a coating material such as lecithin, with the maintain ing of the right particle sizes in the d ispersions or with the use of surfactants.
  • a coating material such as lecithin
  • slow-release formulations can be prepared , by the tech niques and products well-known in the state of the art.
  • the pharmaceutical associations and compositions of the i nvention are extremely effective i n the treatment, prophylactic as wel l as therapeutic, of hyperglycemia, in humans and in animals.
  • Hyperglycemia can be associated or not associated to other pathologies or syndromes and symptoms.
  • the associations and compositions described herein are useful also in the therapeutic treatment of hyperglycemia associated to hyperuricemia.
  • Manifestations such as hyperglycemia and hyperuricemia, individually or in combination, can also be associated to specific syndromes like the metabolic syndrome.
  • metabolic syndrome it is meant a clinical condition accompanied by various manifestations such as obesity.
  • the association described herein can therefore be used in the therapeutic treatment of hyperglycemia associated to hyperuricemia or other pathologies in the context of the metabolic syndrome.
  • Dosage may vary depending on the patient's age and general conditions, the nature and seriousness of the pathology or disorder and of the administration route and type. Dosage should therefore take into account the specific condition to be treated (e.g., hyperglycemia alone or in association with hyperuricemia), the severity of the condition to be treated, the age, weight and general physical conditions of the specific patient, as well as other drugs that the patient is taking, as is well-known to those skilled in the art. Moreover, it is evident that said effective amount may, when required, be lowered or raised according to the responses of the treated patient and/or according to the assessment of the physician prescribing the compounds of the present invention.
  • the specific condition to be treated e.g., hyperglycemia alone or in association with hyperuricemia
  • said effective amount may, when required, be lowered or raised according to the responses of the treated patient and/or according to the assessment of the physician prescribing the compounds of the present invention.
  • compositions for oral use in solid form can contain an amount of xanthine oxidase inhibitor, specifically febuxostat, of between 10 and 200 mg per single dose, and preferably of between 25 and 120 mg, and an amount of metformin, preferably metformin hydrochloride, of between 100 and 1500 mg per single dose, preferably of between 250 and 1000 mg.
  • xanthine oxidase inhibitor specifically febuxostat
  • metformin preferably metformin hydrochloride
  • dosage unit in the present description it is meant the unitary formulation for a single administration, e.g. a tablet, capsule, etc.
  • unit dosage it is meant the amount of active principle for a single administration.
  • compositions of the invention could be prepared according to techniques known in the field, both using the previously prepared association of active principles, and mixing the individual compounds directly during the preparation of the composition.
  • association of active principles may be obtained by a step of mixing metformin or pharmaceutically acceptable salts thereof with the xanthine oxidase inhibitor, febuxostat, or pharmaceutically acceptable salts thereof or polymorphic forms thereof, in a weight ratio comprised between 0.4 and 1 50, or between 2 and 40.
  • the mixture of active principles is formulated in suitable dosage units with one or more pharmaceutically acceptable excipients and additives.
  • Metformin at the dose of 100 mg/kg per os did not significantly modify the hyperglycemic curve in the 5 hours of observation, whereas at the dose of 300 mg/kg per os it reduced by 70% the high blood glucose levels in the period between 2 and 5 hours after administration.
  • Febuxostat, with a single dose of 5 mg/kg per os did not show positive effects on hyperglycemia, whereas coadministration with metformin (100 mg/kg per os) yielded a hypoglycemizing effect comparable to that of metformin at 300 mg/kg per os.
  • febuxostat and metformin yielded maximal results in reducing the high levels of glycemia at the daily doses of 5 mg/kg per os of febuxostat and of 100 mg/kg per os of metformin, comparable to the result obtained with 300 mg/kg per os.
  • tablet for oral administration containing:
  • colloidal silica 0.5 mg
  • tablet for oral administration containing:
  • colloidal silica 0.5 mg
  • tablet for oral administration containing:
  • tablet for oral administration containing:
  • tablet for oral administration containing:

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Abstract

La présente invention a pour objet l'association de principes actifs, c'est-à-dire d'un inhibiteur de la xanthine oxydase avec un dérivé de biguanide, de préférence la metformine, des compositions pharmaceutiques comprenant lesdits principes actifs, destinée à être utilisée dans un traitement thérapeutique humain ou vétérinaire, et des procédés pour sa préparation.
PCT/EP2011/057412 2010-05-10 2011-05-09 Association de l'inhibiteur de la xanthine oxydase fébuxostat et de metformine et son utilisation WO2011141419A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITRM2010A000233 2010-05-10
ITRM2010A000233A IT1400609B1 (it) 2010-05-10 2010-05-10 Associazione di inibitori della xantina ossidasi e metformina e loro uso.

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WO2011141419A1 true WO2011141419A1 (fr) 2011-11-17

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AR (1) AR081024A1 (fr)
CR (1) CR20120617A (fr)
IT (1) IT1400609B1 (fr)
TW (1) TW201206431A (fr)
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220023251A1 (en) * 2018-12-06 2022-01-27 Arthrosi Therapeutics, Inc. Methods for treating or preventing gout or hyperuricemia
WO2024033705A1 (fr) * 2022-08-08 2024-02-15 Xortx Therapeutics, Inc. Formulations d'inhibiteur de xanthine oxydase avec bases organiques
US12145917B2 (en) 2018-12-06 2024-11-19 Arthrosi Therapeutics, Inc. Crystalline forms of a compound for treating or preventing gout or hyperuricemia

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0513379A1 (fr) 1990-11-30 1992-11-19 Teijin Limited Derive de 2-arylthiazole et composition pharmaceutique contenant ce derive
EP1020454A1 (fr) 1998-06-19 2000-07-19 Teijin Limited Modifications polymorphes de 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazole-acide carboxylique et procedes de preparation associes
WO2004060489A2 (fr) 2002-12-20 2004-07-22 Tap Pharmaceutical Products Inc. Traitement de l'insuffisance cardiaque chronique
WO2007019153A2 (fr) 2005-08-03 2007-02-15 Tap Pharmaceutical Products, Inc. Methodes de traitement de l'hypertension
WO2007062028A2 (fr) 2005-11-21 2007-05-31 Tap Pharmaceutical Products, Inc. Traitement d'allongement de l'intervalle qt et maladies associees
WO2008064015A1 (fr) 2006-11-13 2008-05-29 Takeda Pharmaceuticals North America Procédés pour préserver la fonction rénale au moyen d'inhibiteurs de xanthine oxydoréductase
WO2008127893A1 (fr) * 2007-04-04 2008-10-23 Hight H Thomas Compositions pharmaceutiques à base de niacine
WO2008147601A1 (fr) * 2007-04-17 2008-12-04 University Of Florida Research Foundation, Inc. Procédés et compositions pour améliorer une hyperlipidémie induite par thiazidique

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0513379A1 (fr) 1990-11-30 1992-11-19 Teijin Limited Derive de 2-arylthiazole et composition pharmaceutique contenant ce derive
EP1020454A1 (fr) 1998-06-19 2000-07-19 Teijin Limited Modifications polymorphes de 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazole-acide carboxylique et procedes de preparation associes
WO2004060489A2 (fr) 2002-12-20 2004-07-22 Tap Pharmaceutical Products Inc. Traitement de l'insuffisance cardiaque chronique
WO2007019153A2 (fr) 2005-08-03 2007-02-15 Tap Pharmaceutical Products, Inc. Methodes de traitement de l'hypertension
WO2007062028A2 (fr) 2005-11-21 2007-05-31 Tap Pharmaceutical Products, Inc. Traitement d'allongement de l'intervalle qt et maladies associees
WO2008064015A1 (fr) 2006-11-13 2008-05-29 Takeda Pharmaceuticals North America Procédés pour préserver la fonction rénale au moyen d'inhibiteurs de xanthine oxydoréductase
WO2008127893A1 (fr) * 2007-04-04 2008-10-23 Hight H Thomas Compositions pharmaceutiques à base de niacine
WO2008147601A1 (fr) * 2007-04-17 2008-12-04 University Of Florida Research Foundation, Inc. Procédés et compositions pour améliorer une hyperlipidémie induite par thiazidique

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
BUTTURINI, U. ET AL., CLINICA TERAPEUTICA, vol. 77, no. 6, 1976, pages 529 - 541
DASKALOPOULOU S S ET AL: "Effect on serum uric acid levels of drugs prescribed for indications other than treating hyperuricaemia", CURRENT PHARMACEUTICAL DESIGN 2005 NL LNKD- DOI:10.2174/138161205774913309, vol. 11, no. 32, 2005, pages 4161 - 4175, XP002621474, ISSN: 1381-6128 *
DESEATNICOVA E ET AL: "Rosiglitasone in complex therapy of gout", ANNALS OF THE RHEUMATIC DISEASES, vol. 64, no. Suppl. 3, July 2005 (2005-07-01), & ANNUAL EUROPEAN CONGRESS OF RHEUMATOLOGY; VIENNA, AUSTRIA; JUNE 08 11, 2005, pages 501, XP008132804, ISSN: 0003-4967 *
FENSTER B E ET AL: "Endothelial dysfunction: Clinical strategies for treating oxidant stress", AMERICAN HEART JOURNAL 20030801 US LNKD- DOI:10.1016/S0002-8703(02)94796-4, vol. 146, no. 2, 1 August 2003 (2003-08-01), pages 218 - 226, XP002621472, ISSN: 0002-8703 *
HEPBURN A L ET AL: "Long-term remission from gout associated with fenofibrate therapy", CLINICAL RHEUMATOLOGY 200302 GB LNKD- DOI:10.1007/S10067-002-0658-1, vol. 22, no. 1, February 2003 (2003-02-01), pages 73 - 76, XP002621470, ISSN: 0770-3198 *
JOHNSON R J ET AL: "Hypothesis: Could excessive fructose intake and uric acid cause type 2 diabetes?", ENDOCRINE REVIEWS 200902 US LNKD- DOI:10.1210/ER.2008-0033, vol. 30, no. 1, February 2009 (2009-02-01), pages 96 - 116, XP002621473, ISSN: 0163-769X *
REUNGJUI S ET AL: "Thiazide diuretics exacerbate fructose-induced metabolic syndrome", JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY 200710 US LNKD- DOI:10.1681/ASN.2007040416, vol. 18, no. 10, October 2007 (2007-10-01), pages 2724 - 2731, XP002621475, ISSN: 1046-6673 *
SANCHEZ-LOZADA L G ET AL: "Effects of febuxostat on metabolic and renal alterations in rats with fructose-induced metabolic syndrome", AMERICAN JOURNAL OF PHYSIOLOGY - RENAL PHYSIOLOGY 200804 US LNKD- DOI:10.1152/AJPRENAL.00454.2007, vol. 294, no. 4, April 2008 (2008-04-01), pages F710 - F718, XP002621471, ISSN: 0363-6127 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220023251A1 (en) * 2018-12-06 2022-01-27 Arthrosi Therapeutics, Inc. Methods for treating or preventing gout or hyperuricemia
US12145917B2 (en) 2018-12-06 2024-11-19 Arthrosi Therapeutics, Inc. Crystalline forms of a compound for treating or preventing gout or hyperuricemia
WO2024033705A1 (fr) * 2022-08-08 2024-02-15 Xortx Therapeutics, Inc. Formulations d'inhibiteur de xanthine oxydase avec bases organiques

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