WO1998057635A1 - Traitement du diabete a l'aide de thiazolidinedione et d'un inhibiteur des alpha-glucosidases - Google Patents

Traitement du diabete a l'aide de thiazolidinedione et d'un inhibiteur des alpha-glucosidases Download PDF

Info

Publication number
WO1998057635A1
WO1998057635A1 PCT/EP1998/003691 EP9803691W WO9857635A1 WO 1998057635 A1 WO1998057635 A1 WO 1998057635A1 EP 9803691 W EP9803691 W EP 9803691W WO 9857635 A1 WO9857635 A1 WO 9857635A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
administration
glucosidase inhibitor
pharmaceutically acceptable
alpha glucosidase
Prior art date
Application number
PCT/EP1998/003691
Other languages
English (en)
Inventor
Stephen Alistair Smith
Original Assignee
Smithkline Beecham Plc
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
Priority claimed from GBGB9712865.6A external-priority patent/GB9712865D0/en
Priority claimed from GBGB9806708.5A external-priority patent/GB9806708D0/en
Priority to SK1794-99A priority Critical patent/SK179499A3/sk
Priority to EP98939513A priority patent/EP0975343A1/fr
Priority to IL13313898A priority patent/IL133138A0/xx
Priority to JP50375699A priority patent/JP2001523271A/ja
Priority to EA200000040A priority patent/EA200000040A1/ru
Priority to BR9810186-2A priority patent/BR9810186A/pt
Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Priority to CA002294134A priority patent/CA2294134A1/fr
Priority to AU87999/98A priority patent/AU8799998A/en
Priority to APAP/P/1999/001720A priority patent/AP9901720A0/en
Priority to NZ501345A priority patent/NZ501345A/en
Publication of WO1998057635A1 publication Critical patent/WO1998057635A1/fr
Priority to BG103966A priority patent/BG103966A/bg
Priority to NO996270A priority patent/NO996270L/no

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • 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
    • 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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • 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
    • 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

Definitions

  • This invention relates to a method of treatment, in particular to a method for the treatment of diabetes mellitus, especially non-insulin dependent diabetes (NIDDM) or Type II diabetes and conditions associated with diabetes mellitus.
  • NIDDM non-insulin dependent diabetes
  • Alpha glucosidase inhibitor antihyperglycaemic agents such as Acarbose, Emiglitate and Miglitol, are commonly used in the treatment of NIDDM (or Type II diabetes).
  • European Patent Application, Publication Number 0,306,228 relates to certain thiazolidinedione derivatives disclosed as having antihyperglycaemic and hypolipidaemic activity.
  • One particular thiazolidinedione disclosed in EP 0306228 is 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione (hereinafter 'Compound (I)').
  • WO94/05659 discloses certain salts of Compound (I) including the maleate salt at example 1 thereof.
  • Compound (I) is an example of a class of anti-hyperglycaemic agents known as 'insulin sensitisers'.
  • Compound (I) is a thiazolidinedione insulin sensitiser.
  • Another series of compounds generally recognised as having insulin sensitiser activity are those typified by the compounds disclosed in International Patent Applications, Publication Numbers WO93/21166 and WO94/01420. These compounds are herein referred to as 'acyclic insulin sensitisers'.
  • Other examples of acyclic insulin sensitisers are those disclosed in United States Patent Number 5232945 and International Patent Applications, Publication Numbers WO92/03425 and WO91/19702. Examples of other insulin sensitisers are those disclosed in European Patent
  • Compound (I) in combination with an alpha glucosidase inhibitor antihyperglycaemic agent provides a particularly beneficial effect on glycaemic control, with minimal adverse side effects, such combination is therefore particularly useful for the treatment of diabetes mellitus, especially Type II diabetes and conditions associated with diabetes mellitus.
  • the invention provides a method for the treatment of diabetes mellitus, especially Type II diabetes and conditions associated with diabetes mellitus in a mammal such as a human, which method comprises administering an effective non-toxic and pharmaceutically acceptable amount of an insulin sensitiser, such as Compound (I), and an alpha glucosidase inhibitor antihyperglycaemic agent, to a mammal in need thereof.
  • an insulin sensitiser such as Compound (I)
  • an alpha glucosidase inhibitor antihyperglycaemic agent an effective non-toxic and pharmaceutically acceptable amount of an insulin sensitiser, such as Compound (I), and an alpha glucosidase inhibitor antihyperglycaemic agent
  • the invention provides an insulin sensitiser, such as Compound (I), together with an alpha glucosidase inhibitor antihyperglycaemic agent for use in a method for the treatment of diabetes mellitus, especially Type II diabetes and conditions associated with diabetes mellitus.
  • an insulin sensitiser such as Compound (I)
  • an alpha glucosidase inhibitor antihyperglycaemic agent for use in a method for the treatment of diabetes mellitus, especially Type II diabetes and conditions associated with diabetes mellitus.
  • the method comprises either co-administration of an insulin sensitiser, such as Compound (I), and an alpha glucosidase inhibitor antihyperglycaemic agent or the sequential administration thereof.
  • an insulin sensitiser such as Compound (I)
  • an alpha glucosidase inhibitor antihyperglycaemic agent or the sequential administration thereof.
  • Co-administration includes administration of a formulation which includes both an insulin sensitiser, such as Compound (I), and a biguanide antihyperglycaemic agent or the essentially simultaneous administration of separate formulations of each agent.
  • an insulin sensitiser such as Compound (I)
  • an alpha glucosidase inhibitor antihyperglycaemic agent for use in the manufacture of a composition for the treatment of diabetes mellitus, especially Type II diabetes and conditions associated with diabetes mellitus.
  • a suitable thiazolidinedione insulin sensitiser is Compound (I).
  • Other suitable thiazolidinedione insulin sensitisers include (+) -5-[[4-[(3,4- dihydro-6-hydroxy-2,5J,8-tetramethyl-2H-l-benzopyran-2- yl)methoxy]phenyl]methyl]-2,4-thiazolidinedione (or troglitazone), 5-[4-[(l- methylcyclohexyl)methoxy]benzyl] thiazolidine-2,4-dione (or ciglitazone), 5-[4-[2-(5- ethylpyridin-2-yl)ethoxy]benzyl] thiazolidine-2,4-dione (or pioglitazone) or 5-[(2- benzyl-2,3-dihydrobenzopyran)-5-ylmethyl)thiazolidine-2,4-dione (or eng
  • the method comprises the administration of 2 to 12 mg of Compound (I), especially when administered per day.
  • the method comprises the administration of 2 to 4 , 4 to 8 or 8 to Particularly, the method comprises the administration of 2 to 4mg of Compound (I), especially when administered per day.
  • the method comprises the administration of 4 to 8mg of Compound (I), especially when administered per day.
  • the method comprises the administration of 8 to 12 mg of
  • Compound (I) especially when administered per day.
  • the method comprises the administration of 2 mg of Compound (I), especially when administered per day.
  • the method comprises the administration of 4 mg of Compound (I), especially when administered per day.
  • the method comprises the administration of 8 mg of Compound (I), especially when administered per day.
  • the insulin sensitiser such as Compound (I) and the alpha glucosidase inhibitor antihyperglycaemic agent are each administered in a pharmaceutically acceptable form, including pharmaceutically acceptable derivatives such as pharmaceutically acceptable salts, esters and solvates thereof, as appropriate of the relevant pharmaceutically active agent.
  • pharmaceutically acceptable derivatives such as pharmaceutically acceptable salts, esters and solvates thereof, as appropriate of the relevant pharmaceutically active agent.
  • the names used for the relevant alpha glucosidase inhibitor may relate to a particular pharmaceutical form of the relevant active agent: It will be understood that all pharmaceutically acceptable forms of the active agents per se are encompassed by this invention.
  • Suitable pharmaceutically acceptable forms of insulin sensitisers include those described in the above mentioned publications.
  • Suitable pharmaceutically acceptable salted forms of Compound (I) include those described in EP 0306228 and WO94/05659.
  • a preferred pharmaceutically acceptable salt is a maleate.
  • Suitable pharmaceutically acceptable solvated forms of Compound (I) include those described in EP 0306228 and WO94/05659, in particular hydrates.
  • Suitable pharmaceutically acceptable forms of the alpha glucosidase inhibitor antihyperglycaemic agent depend upon the particular agent used but includes known pharmaceutically acceptable forms of the particular compound chosen. Such derivatives are found or are referred to in standard reference texts such as the British and US Pharmacopoeias, Remington's Pharmaceutical Sciences (Mack Publishing Co.) and Martindale The Extra Pharmacopoeia (London, The Pharmaceutical Press) (for example see the 31st Edition page 341 and pages cited therein).
  • the insulin sensitisers may be prepared using known methods, for example those disclosed in the above mentioned publications which are incorporated herein by reference.
  • Compound (I) or, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof may be prepared using known methods, for example those disclosed in EP 0306228 and WO94/05659. The disclosures of EP 0306228 and WO94/05659 are incorporated herein by reference.
  • Compound (I) may exist in one of several tautomeric forms, all of which are encompassed by the term Compound (I) as individual tautomeric forms or as mixtures thereof.
  • Compound (I) contains a chiral carbon atom, and hence can exist in up to two stereoisomeric forms, the term Compound (I) encompasses all of these isomeric forms whether as individual isomers or as mixtures of isomers, including racemates.
  • the alpha glucosidase inhibitor antihyperglycaemic agent of choice is prepared according to known methods, such methods are found or are referred to in standard reference texts, such as the British and US Pharmacopoeias, Remington's Pharmaceutical Sciences (Mack Publishing Co.) and Martindale The Extra Pharmacopoeia (London, The Pharmaceutical Press) (for example see the 31st Edition page 341 and pages cited therein).
  • condition associated with diabetes includes those conditions associated with the pre-diabetic state, conditions associated with diabetes mellitus itself and complications associated with diabetes mellitus.
  • condition associated with the pre-diabetic state' includes conditions such as insulin resistance, including hereditary insulin resistance, impaired glucose tolerance, obesity and hyperinsulinaemia.
  • diabetes mellitus itself include hyperglycaemia, insulin resistance, including acquired insulin resistance and obesity. Further conditions associated with diabetes mellitus itself include hypertension and cardiovascular disease, especially atherosclerosis and conditions associated with insulin resistance. Conditions associated with insulin resistance include polycystic ovarian syndrome and steroid induced insulin resistance and gestational diabetes.
  • Renal diseases associated with Type II diabetes include nephropathy, glomerulonephritis, glomerular sclerosis, nephrotic syndrome, hypertensive nephrosclerosis and end stage renal disease.
  • the term 'pharmaceutically acceptable embraces both human and veterinary use: for example the term 'pharmaceutically acceptable' embraces a veterinarily acceptable compound.
  • scalar amounts including mg amounts, of Compound (I) in a pharmaceutically acceptable form
  • the scalar amount referred to is made in respect of Compound (I) per se:
  • 2 mg of Compound (I) in the form of the maleate salt is that amount of maleate salt which contains 2 mg of Compound (I).
  • Diabetes mellitus is preferably Type II diabetes.
  • the particularly beneficial effect on glycaemic control provided by the treatment of the invention is indicated to be a synergistic effect relative to the control expected for the sum of the effects of the individual active agents.
  • Glycaemic control may be characterised using conventional methods, for example by measurement of a typically used index of glycaemic control such as fasting plasma glucose or glycosylated haemoglobin (Hb Ale). Such indices are determined using standard methodology, for example those described in: Tuescher A, Richterich, P., Sau. med. Wschr. 101 (1971), 345 and 390 and Frank P., 'Monitoring the Diabetic Patent with Glycosolated Hemoglobin Measurements', Clinical Products 1988
  • the dosage level of each of the active agents when used in accordance with the treatment of the invention will be less than would have been required from a purely additive effect upon glycaemic control.
  • the treatment of the invention will effect an improvement, relative to the individual agents, in the levels of advanced glycosylation end products (AGEs), leptin and serum lipids including total cholesterol, HDL- cholesterol, LDL-cholesterol including improvements in the ratios thereof, in particular an improvement in serum lipids including total cholesterol, HDL- cholesterol, LDL-cholesterol including improvements in the ratios thereof.
  • AGEs advanced glycosylation end products
  • leptin and serum lipids including total cholesterol, HDL- cholesterol, LDL-cholesterol including improvements in the ratios thereof, in particular an improvement in serum lipids including total cholesterol, HDL- cholesterol, LDL-cholesterol including improvements in the ratios thereof.
  • the active medicaments are preferably administered in pharmaceutical composition form.
  • such compositions can include both medicaments or one only of the medicaments.
  • compositions comprising an insulin sensitisers, such as Compound (I) especially 2 to 12 mg thereof, an alpha glucosidase inhibitor antihyperglycaemic agent and a pharmaceutically acceptable carrier therefor.
  • an insulin sensitisers such as Compound (I) especially 2 to 12 mg thereof, an alpha glucosidase inhibitor antihyperglycaemic agent and a pharmaceutically acceptable carrier therefor.
  • compositions are adapted for oral administration. However, they may be adapted for other modes of administration, for example parenteral administration, sublingual or transdermal administration.
  • compositions may be in the form of tablets, capsules, powders, granules, lozenges, suppositories, reconstitutable powders, or liquid preparations, such as oral or sterile parenteral solutions or suspensions.
  • a composition of the invention is in the form of a unit dose.
  • Unit dose presentation forms for oral administration may be tablets and capsules and may contain conventional excipients such as binding agents, for example syrup, acacia, gelatin, sorbitol, tragacanth, or polyvinylpyrrolidone; fillers, for example lactose, sugar, maize-starch, calcium phosphate, sorbitol or glycine; tabletting lubricants, for example magnesium stearate; disintegrants, for example starch, polyvinylpyrrolidone, sodium starch glycollate or microcrystalline cellulose; or pharmaceutically acceptable wetting agents such as sodium lauryl sulphate.
  • the compositions are preferably in a unit dosage form in an amount appropriate for the relevant daily dosage.
  • Suitable dosages including unit dosages of the Compound of formula (I) comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 mg of Compound (I).
  • the medicaments may be administered from 1 to 6 times a day, but most preferably 1 or 2 times per day.
  • Particular dosages of Compound (I) are 2mg/day, 4mg/day, including 2mg twice per day, and 8 mg/day, including 4mg twice per day.
  • Suitable dosages including unit dosages of the insulin sensitisers and the alpha glucosidase inhibitor antihyperglycaemic agent include the known dosages and unit doses for these compounds as described or referred to in reference texts such as the British and US Pharmacopoeias, Remington's Pharmaceutical Sciences (Mack Publishing Co.), Martindale The Extra Pharmacopoeia (London, The Pharmaceutical Press) (for example see the 31st Edition page 341 and pages cited therein) or the above mentioned publications.
  • a typical daily dosage of acarbose is in the range of from 50 to 600 mg, an example lOOmg or 200mg per day.
  • the solid oral compositions may be prepared by conventional methods of blending, filling or tabletting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are of course conventional in the art.
  • the tablets may be coated according to methods well known in normal pharmaceutical practice, in particular with an enteric coating.
  • Oral liquid preparations may be in the form of, for example, emulsions, syrups, or elixirs, or may be presented as a dry product for reconstitution with water or other suitable vehicle before use.
  • Such liquid preparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminium stearate
  • gel hydrogenated edible fats
  • emulsifying agents for example lecithin, sorbitan monooleate, or acacia
  • non-aqueous vehicles which may include edible oils
  • almond oil fractionated coconut oil
  • oily esters such as esters of glycerine, propylene glycol, or ethyl alcohol
  • preservatives for example methyl or propyl p-hydroxybenzoate or sorbic acid
  • conventional flavouring or colouring agents for example methyl or propyl p-hydroxybenzoate or sorbic acid.
  • fluid unit dosage forms are prepared utilizing the compound and a sterile vehicle, and, depending on the concentration used, can be either suspended or dissolved in the vehicle.
  • the compound can be dissolved in water for injection and filter sterilized before filling into a suitable vial or ampoule and sealing.
  • adjuvants such as a local anaesthetic, a preservative and buffering agents can be dissolved in the vehicle.
  • the composition can be frozen after filling into the vial and the water removed under vacuum.
  • Parenteral suspensions are prepared in substantially the same manner, except that the Compound (I)s suspended in the vehicle instead of being dissolved, and sterilization cannot be accomplished by filtration.
  • the compound can be sterilized by exposure to ethylene oxide before suspending in the sterile vehicle.
  • a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound.
  • Compositions may contain from 0.1% to 99% by weight, preferably from 10-60% by weight, of the active material, depending upon the method of administration.
  • compositions may, if desired, be in the form of a pack accompanied by written or printed instructions for use.
  • compositions are formulated according to conventional methods, such as those disclosed in standard reference texts, for example the British and US
  • the present invention also provides a pharmaceutical composition
  • a pharmaceutical composition comprising Compound (I), especially 2 to 12 mg thereof, an alpha glucosidase inhibitor antihyperglycaemic agent and a pharmaceutically acceptable carrier therefor, for use as an active therapeutic substance.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising Compound (I), especially 2 to 12 mg thereof, an alpha glucosidase inhibitor antihyperglycaemic agent and a pharmaceutically acceptable carrier therefor, for use in the treatment of diabetes mellitus, especially Type II diabetes and conditions associated with diabetes mellitus.
  • a range of 2 to 4mg includes a range of 2.1 to 4, 2.2 to 4, 2.3 to 4, 2.4 to 4, 2.5 to 4, 2.6 to 4, 2.7 to 4, 2.8 to 4, 2.9 to 4 or 3 to 4mg.
  • a range of 4 to 8mg includes a range of 4.1 to 8, 4.2 to 8, 4.3 to 8, 4.4 to 8, 4.5 to 8, 4.6 to 8, 4.7 to 8, 4.8 to 8, 4.9 to 8, 5 to 8, 6 to 8 or 7 to 8mg.
  • a range of 8 to 12 mg includes a range of 8.1 to 12, 8.2 to 12, 8.3 to 12, 8.4 to 12, 8.5 to 12, 8.6 to 12, 8.7 to 12, 8.8 to 12, 8.9 to 12, 9 to 12, 10 to 12 or 11 to 12mg.
  • lactose monohydrate is passed through a suitable screen and blended with the milled maleate salt of Compound (I).
  • Sodium starch glycollate, hydoxypropyl methylcellulose, microcrystalline cellulose and the remaining lactose are passed through a suitable screen and added to the mixture. Blending is then continued.
  • the resulting mixture is then wet granulated with purified water.
  • the wet granules are then screened, dried on a fluid bed drier and the dried granules are passed through a further screen and finally homogenised.
  • the granules from above are placed into a tumble blender. Approximately two thirds of the lactose is screened and added to the blender. The microcrystalline cellulose, sodium starch glycollate, magnesium stearate and remaining lactose are screened and added to the blender and the mixture blended together. The resulting mix is then compressed on a rotary tablet press to a target weight of 150mg for the 1 , 2 and 4mg tablets and to a target weight of 300mg for the 8mg tablets.
  • the tablet cores are then transferred to a tablet coating machine, pre-warmed with warm air (approximately 65 °C) and film coated until the tablet weight has increased by 2.0% to 3.5%.
  • Aqueous film coating material 4.5 4.5 4.5 9.0

Abstract

L'invention concerne une méthode de traitement, chez un mammifère, du diabète sucré et des états associés à ce diabète, cette méthode consistant à administrer à un mammifère nécessitant un tel traitement, une dose efficace, non toxique et acceptable sur le plan pharmacologique, d'un agent de sensibilisation à l'insuline et d'un agent anti-hyperglycémiant inhibant les alpha-glucosidases.
PCT/EP1998/003691 1997-06-18 1998-06-15 Traitement du diabete a l'aide de thiazolidinedione et d'un inhibiteur des alpha-glucosidases WO1998057635A1 (fr)

Priority Applications (12)

Application Number Priority Date Filing Date Title
AU87999/98A AU8799998A (en) 1997-06-18 1998-06-15 Treatment of diabetes with thiazolidinedione and alpha-glucosidase inhibitor
APAP/P/1999/001720A AP9901720A0 (en) 1997-06-18 1998-06-15 Treatment of diabetes with thiazolidinedione and alpha-glucosidase inhibitors.
CA002294134A CA2294134A1 (fr) 1997-06-18 1998-06-15 Traitement du diabete a l'aide de thiazolidinedione et d'un inhibiteur des alpha-glucosidases
IL13313898A IL133138A0 (en) 1997-06-18 1998-06-15 Treatment of diabetes with thiazolidinedione and alpha-glucosidase inhibitor
JP50375699A JP2001523271A (ja) 1997-06-18 1998-06-15 チアゾリジンジオンおよびアルファ−グルコシダーゼ阻害剤を用いる糖尿病の治療
EA200000040A EA200000040A1 (ru) 1997-06-18 1998-06-15 Способ лечения диабета тиазолидиндионом и ингибитором альфа-глюкозидазы
BR9810186-2A BR9810186A (pt) 1997-06-18 1998-06-15 Tratamento de diabete com tiazolidinadiona e inibidor de alfa-glicosidade
SK1794-99A SK179499A3 (en) 1997-06-18 1998-06-15 The use of insulin sensitiser and alpha-glucosidase inhibitive antihyperglycaemic agent
EP98939513A EP0975343A1 (fr) 1997-06-18 1998-06-15 Traitement du diabete a l'aide de thiazolidinedione et d'un inhibiteur des alpha-glucosidases
NZ501345A NZ501345A (en) 1997-06-18 1998-07-15 Treatment of diabetes mellitus with 5-[4-[2-(N-methyl-N-(2- pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione (2-12 mg) and an alpha-glucosidase inhibitor antihyperglycemic agent
BG103966A BG103966A (bg) 1997-06-18 1999-12-08 Лечение на диабет с тиазолидиндион и инхибитор наалфа глюкозидазата
NO996270A NO996270L (no) 1997-06-18 1999-12-17 Behandling av diabetes med tiazolidindion og <alfa>- glukosidaseinhibitor

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB9712865.6 1997-06-18
GBGB9712865.6A GB9712865D0 (en) 1997-06-18 1997-06-18 Novel method of treatment
GB9806708.5 1998-03-27
GBGB9806708.5A GB9806708D0 (en) 1998-03-27 1998-03-27 Novel method

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US09445951 A-371-Of-International 1999-12-15
US09/863,136 Continuation US20010034356A1 (en) 1997-06-18 2001-05-23 Treatment of diabetes with thiazolidinedione and alpha-glucosidase inhibitor

Publications (1)

Publication Number Publication Date
WO1998057635A1 true WO1998057635A1 (fr) 1998-12-23

Family

ID=26311746

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/003691 WO1998057635A1 (fr) 1997-06-18 1998-06-15 Traitement du diabete a l'aide de thiazolidinedione et d'un inhibiteur des alpha-glucosidases

Country Status (24)

Country Link
EP (1) EP0975343A1 (fr)
JP (1) JP2001523271A (fr)
KR (1) KR20010013845A (fr)
CN (1) CN1274282A (fr)
AP (1) AP9901720A0 (fr)
AR (2) AR014881A1 (fr)
AU (1) AU8799998A (fr)
BG (1) BG103966A (fr)
BR (1) BR9810186A (fr)
CA (1) CA2294134A1 (fr)
CO (1) CO4940453A1 (fr)
DZ (1) DZ2519A1 (fr)
EA (1) EA200000040A1 (fr)
IL (1) IL133138A0 (fr)
MA (1) MA26510A1 (fr)
NO (1) NO996270L (fr)
NZ (1) NZ501345A (fr)
OA (1) OA11631A (fr)
PE (1) PE89199A1 (fr)
PL (1) PL337577A1 (fr)
SK (1) SK179499A3 (fr)
TR (1) TR199903072T2 (fr)
UY (1) UY25051A1 (fr)
WO (1) WO1998057635A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2832930A1 (fr) * 2001-12-03 2003-06-06 Lipha Composition pharmaceutique comprenant un inhibiteur d'alpha-glucosidase et un derive de thiazolidinedione et son utilisation pour la preparation de medicaments destines a traiter le diabete
EP1903043A1 (fr) 1999-04-23 2008-03-26 SmithKline Beecham P.L.C. Nouveau composé pharmaceutique
US8183213B2 (en) 2001-04-04 2012-05-22 Ortho Mcneil Pharmaceutical, Inc. Combination therapy comprising glucose reabsorption inhibitors and retinoid-X receptor modulators
US8278268B2 (en) 2001-04-04 2012-10-02 Ortho-Mcneil Pharmaceutical, Inc. Combination therapy comprising glucose reabsorption inhibitors and PPAR modulators

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004067575A (ja) * 2002-08-06 2004-03-04 Yaizu Suisankagaku Industry Co Ltd 糖尿病治療薬効果促進剤
CN101121004B (zh) * 2006-08-08 2010-07-21 鲁南制药集团股份有限公司 含有胰岛素增敏剂和米格列醇的药物组合物
CN101584688B (zh) * 2008-05-24 2010-11-10 鲁南制药集团股份有限公司 一种治疗糖尿病及其并发症的药物组合物
CN101584705B (zh) * 2008-05-24 2010-10-27 鲁南制药集团股份有限公司 一种治疗糖尿病及其并发症的药物组合物

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993003724A1 (fr) * 1991-08-26 1993-03-04 The Upjohn Company Composition pharmaceutique contenant de l'acide 3-guanidinopropionique ainsi que du glibenclamide ou glimepiride de pioglitazone
WO1996009823A1 (fr) * 1994-09-28 1996-04-04 Shaman Pharmaceuticals, Inc. Agent hypoglycemiant derive de cryptolepis
EP0749751A2 (fr) * 1995-06-20 1996-12-27 Takeda Chemical Industries, Ltd. Composition pharmaceutique pour utilisation dans le traitement du diabète

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993003724A1 (fr) * 1991-08-26 1993-03-04 The Upjohn Company Composition pharmaceutique contenant de l'acide 3-guanidinopropionique ainsi que du glibenclamide ou glimepiride de pioglitazone
WO1996009823A1 (fr) * 1994-09-28 1996-04-04 Shaman Pharmaceuticals, Inc. Agent hypoglycemiant derive de cryptolepis
EP0749751A2 (fr) * 1995-06-20 1996-12-27 Takeda Chemical Industries, Ltd. Composition pharmaceutique pour utilisation dans le traitement du diabète
EP0861666A2 (fr) * 1995-06-20 1998-09-02 Takeda Chemical Industries, Ltd. Composition pharmaceutique pour utilisation dans le traitement du diabète

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BRESSLER R ET AL: "ORAL ANTIDIABETIC DRUG USE IN THE ELDERLY", DRUGS AND AGING, vol. 9, no. 6, 1996, pages 418 - 437, XP002064290 *
SCHEEN AJ ET AL: "Oral antidiabetic agents. A guide to selection.", DRUGS, FEB 1998, 55 (2) P225-36, NEW ZEALAND, XP002080821 *
SCHEEN AJ: "Drug treatment of non-insulin-dependent diabetes mellitus in the 1990s. Achievements and future developments.", DRUGS, SEP 1997, 54 (3) P355-68, NEW ZEALAND, XP002080822 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1903043A1 (fr) 1999-04-23 2008-03-26 SmithKline Beecham P.L.C. Nouveau composé pharmaceutique
US8183213B2 (en) 2001-04-04 2012-05-22 Ortho Mcneil Pharmaceutical, Inc. Combination therapy comprising glucose reabsorption inhibitors and retinoid-X receptor modulators
US8278268B2 (en) 2001-04-04 2012-10-02 Ortho-Mcneil Pharmaceutical, Inc. Combination therapy comprising glucose reabsorption inhibitors and PPAR modulators
FR2832930A1 (fr) * 2001-12-03 2003-06-06 Lipha Composition pharmaceutique comprenant un inhibiteur d'alpha-glucosidase et un derive de thiazolidinedione et son utilisation pour la preparation de medicaments destines a traiter le diabete
WO2003047627A1 (fr) * 2001-12-03 2003-06-12 Merck Patent Gmbh Composition pharmaceutique comprenant un inhibiteur de l'alpha-glucosidase ainsi qu'un derive de la thiazolidinedione, et son utilisation pour traiter le diabete

Also Published As

Publication number Publication date
KR20010013845A (ko) 2001-02-26
IL133138A0 (en) 2001-03-19
SK179499A3 (en) 2000-11-07
NO996270D0 (no) 1999-12-17
BR9810186A (pt) 2000-08-08
AR014881A1 (es) 2001-04-11
MA26510A1 (fr) 2004-12-20
EP0975343A1 (fr) 2000-02-02
NZ501345A (en) 2001-10-26
OA11631A (en) 2004-11-22
AU8799998A (en) 1999-01-04
CN1274282A (zh) 2000-11-22
DZ2519A1 (fr) 2003-02-01
EA200000040A1 (ru) 2000-08-28
PL337577A1 (en) 2000-08-28
BG103966A (bg) 2000-07-31
JP2001523271A (ja) 2001-11-20
AR013352A1 (es) 2000-12-27
UY25051A1 (es) 2000-09-29
CA2294134A1 (fr) 1998-12-23
PE89199A1 (es) 1999-10-23
AP9901720A0 (en) 1999-12-31
NO996270L (no) 1999-12-17
TR199903072T2 (xx) 2000-07-21
CO4940453A1 (es) 2000-07-24

Similar Documents

Publication Publication Date Title
AP1279A (en) Treatment of diabetes with thiazolidinedione and metformin.
US20030109553A1 (en) Treatment of diabetes with thiazolidinedione and metformin
EP1001783B1 (fr) Traitement du diabete avec du thiazolidinedione, un secretagogue d&#39;insuline et du biguanide
US20010049380A1 (en) Treatment of diabetes with thiazolidinedione and sulphonylurea
WO1998057635A1 (fr) Traitement du diabete a l&#39;aide de thiazolidinedione et d&#39;un inhibiteur des alpha-glucosidases
WO1999003478A1 (fr) Traitement du diabete avec du thiazolidinedione, un secretagogue d&#39;insuline et un inhibiteur d&#39;alpha glucosidase
WO1998057649A1 (fr) Traitement du diabete a l&#39;aide de thiazolidinedione et de sulfonyluree
US20020123514A1 (en) Treatment of diabetes with thiazolidinedione and alpha-glucosidase inhibitor
AU778947B2 (en) Treatment of diabetes with thiazolidinedione and metformin
NZ515554A (en) Treatment of diabetes with thiazolidinedione and metformin
CA2549864A1 (fr) Traitement du diabete a l&#39;aide de thiazolidinedione et de metformine
AU1540002A (en) Treatment of diabetes with thiazolidinedione and sulphonylurea
MXPA99012098A (en) Treatment of diabetes with thiazolidinedione and alpha-glucosidase inhibitor
MXPA99012078A (en) Treatment of diabetes with thiazolidinedione and metformin
AU2928002A (en) Treatment of diabetes with thiazolidinedione, insulin secretagogue and diguanide

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 133138

Country of ref document: IL

Ref document number: 98806319.0

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH GM GW HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 1998939513

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 501345

Country of ref document: NZ

Ref document number: 87999/98

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 1999/03072

Country of ref document: TR

WWE Wipo information: entry into national phase

Ref document number: PV1999-4580

Country of ref document: CZ

Ref document number: 09445951

Country of ref document: US

ENP Entry into the national phase

Ref document number: 2294134

Country of ref document: CA

Ref document number: 2294134

Country of ref document: CA

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 179499

Country of ref document: SK

Ref document number: 1019997011866

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: PA/a/1999/012098

Country of ref document: MX

Ref document number: 1199901078

Country of ref document: VN

WWE Wipo information: entry into national phase

Ref document number: 200000040

Country of ref document: EA

WWP Wipo information: published in national office

Ref document number: 1998939513

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWP Wipo information: published in national office

Ref document number: 1019997011866

Country of ref document: KR

WWP Wipo information: published in national office

Ref document number: PV1999-4580

Country of ref document: CZ

WWW Wipo information: withdrawn in national office

Ref document number: 1019997011866

Country of ref document: KR

WWW Wipo information: withdrawn in national office

Ref document number: 1998939513

Country of ref document: EP

WWR Wipo information: refused in national office

Ref document number: PV1999-4580

Country of ref document: CZ