EP0999837A1 - Treatment of diabetes with rosiglitazone and insulin - Google Patents
Treatment of diabetes with rosiglitazone and insulinInfo
- Publication number
- EP0999837A1 EP0999837A1 EP98932169A EP98932169A EP0999837A1 EP 0999837 A1 EP0999837 A1 EP 0999837A1 EP 98932169 A EP98932169 A EP 98932169A EP 98932169 A EP98932169 A EP 98932169A EP 0999837 A1 EP0999837 A1 EP 0999837A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- compound
- administration
- insulin
- pharmaceutically acceptable
- diabetes
- 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.)
- Withdrawn
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
- A61K31/33—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
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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
- Insulin is a front line treatment agent for Type I diabetes (or Insulin Dependent Diabetes). It is also used as an antihyperglycaemic agent in the treatment ofNIDDM.
- 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.
- 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 Compound (I) and insulin, to a mammal in need thereof.
- the amount of Compound (I) administered is up to 12 mg, especially when administered per day.
- the method comprises either co-administration of Compound (I) and insulin or the sequential administration thereof.
- Co-administration includes administration of a formulation which includes both an insulin sensitiser, such as Compound (I), and insulin or, more suitably, the essentially simultaneous administration of separate formulations of each agent.
- an insulin sensitiser such as Compound (I)
- insulin or, more suitably, the essentially simultaneous administration of separate formulations of each agent.
- the method comprises the administration of 2 to 12 mg of Compound (I), especially when admimstered per day.
- the method comprises the administration of 2 to 4 , 4 to 8 or 8 to 12 mg of Compound (I) per day.
- 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, such as greater than 4 for example 4.1, to 8 mg, 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
- 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.
- Compound (I) and the insulin are each administered in a pharmaceutically acceptable form, including for Compound (I), pharmaceutically acceptable derivatives such as pharmaceutically acceptable salts and solvates thereof.
- 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 insulin 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).
- 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 one or more stereoisomeric forms, the term Compound (I) encompasses all of these isomeric forms whether as individual isomers or as mixtures of isomers, including racemates.
- Insulin 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 conditions associated with diabetes mellitus itself and complications associated with diabetes mellitus.
- 'Conditions associated with 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 poly cystic ovarian syndrome and steroid induced insulin resistance and gestational diabetes. 'Complications associated with diabetes mellitus' includes renal disease, especially renal disease associated with Type II diabetes, neuropathy and retinopathy.
- Renal diseases associated with Type II diabetes include nephropathy, glomerulonephritis, glomerular sclerosis, nephrotic syndrome, hypertensive nephrosclerosis and end stage renal disease.
- nephropathy glomerulonephritis
- glomerular sclerosis glomerular sclerosis
- nephrotic syndrome hypertensive nephrosclerosis
- end stage renal disease 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 active medicaments are preferably administered in pharmaceutical composition form.
- such compositions can include both medicaments or one only of the medicaments.
- compositions, formulations and methods of administration suitably refer to the compositions, formulations and administration of Compound (I).
- compositions are adapted for oral administration. However, they may be adapted for other modes of administration, for example parenteral administration, sublingual or transdermal administration.
- the 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.
- 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 glycoUate or microcrystalline cellulose; or pharmaceutically acceptable wetting agents such as sodium lauryl sulphate.
- 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 star
- 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), for example 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; and if desired conventional flavouring or colouring agents.
- suspending agents for example sorbitol, syrup, methyl cellulose,
- 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 herein and in standard reference texts, for example 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) and Harry's Cosmeticology (Leonard Hill Books).
- 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 two medicaments may be administered from 1 to 6 times a day, but most preferably 1 or 2 times per day.
- Suitable dosages of insulin include those described or referred to in 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).
- 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,
- 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. No adverse toxicological effects have been established for the compositions or methods of the invention in the abovementioned dosage ranges.
- lactose monohydrate is passed through a suitable screen and blended with the milled maleate salt of Compound (I).
- Sodium starch glycoUate, 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 glycoUate, 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
Landscapes
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Emergency Medicine (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9712866.4A GB9712866D0 (en) | 1997-06-18 | 1997-06-18 | Novel method of treatment |
GB9712866 | 1997-06-18 | ||
PCT/EP1998/003692 WO1998057636A1 (en) | 1997-06-18 | 1998-06-15 | Treatment of diabetes with rosiglitazone and insulin |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0999837A1 true EP0999837A1 (en) | 2000-05-17 |
Family
ID=10814527
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP98932169A Withdrawn EP0999837A1 (en) | 1997-06-18 | 1998-06-15 | Treatment of diabetes with rosiglitazone and insulin |
Country Status (30)
Country | Link |
---|---|
EP (1) | EP0999837A1 (no) |
JP (1) | JP2002504138A (no) |
KR (1) | KR20010013843A (no) |
CN (1) | CN1133431C (no) |
AP (1) | AP1287A (no) |
AR (2) | AR015894A1 (no) |
AU (1) | AU8216398A (no) |
BG (1) | BG104059A (no) |
BR (1) | BR9810444A (no) |
CA (1) | CA2294141A1 (no) |
CO (1) | CO4940454A1 (no) |
DZ (1) | DZ2521A1 (no) |
EA (1) | EA004800B1 (no) |
GB (1) | GB9712866D0 (no) |
HU (1) | HUP0003260A3 (no) |
ID (1) | ID23951A (no) |
IL (1) | IL133143A0 (no) |
IN (1) | IN189723B (no) |
MA (1) | MA26511A1 (no) |
NO (1) | NO996265D0 (no) |
OA (1) | OA11517A (no) |
PE (1) | PE104499A1 (no) |
PL (1) | PL343123A1 (no) |
SK (1) | SK179399A3 (no) |
TR (1) | TR199903095T2 (no) |
TW (1) | TW587937B (no) |
UA (1) | UA70299C2 (no) |
UY (1) | UY25050A1 (no) |
WO (1) | WO1998057636A1 (no) |
ZA (1) | ZA985237B (no) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6291495B1 (en) * | 1997-02-24 | 2001-09-18 | Robert B. Rieveley | Method and composition for the treatment of diabetes |
TWI249401B (en) | 1999-04-14 | 2006-02-21 | Takeda Chemical Industries Ltd | Agent for improving ketosis |
BR0009934A (pt) | 1999-04-23 | 2002-06-04 | Smithkline Beecham Plc | Produto farmacêutico |
EP1849475A1 (en) * | 1999-06-21 | 2007-10-31 | Eli Lilly & Company | Synergistic use of thiazolidinediones with glucagon-like peptide-1 and agonists thereof to treat non-insulin dependent diabetes |
WO2001000223A2 (en) * | 1999-06-25 | 2001-01-04 | Minimed Inc. | Multiple agent diabetes therapy |
US6468507B1 (en) * | 2000-05-01 | 2002-10-22 | Aeropharm Technology, Inc. | Non-aqueous aerosol formulation comprising rosiglitazone maleate, a non-aqueous carrier, and an amino acid stabilizer |
GB0023970D0 (en) * | 2000-09-29 | 2000-11-15 | Smithkline Beecham Plc | Novel pharmaceutical |
WO2002067969A2 (en) | 2001-02-21 | 2002-09-06 | Medtronic Minimed, Inc. | Stabilized insulin formulations |
US6531461B1 (en) | 2001-06-04 | 2003-03-11 | Louis Obyo Obyo Nelson | Medicament for the treatment of diabetes |
US20020198203A1 (en) * | 2001-06-07 | 2002-12-26 | Wyeth | Combination of a PTPase inhibitor and a thiazolidinedione agent |
US6737401B2 (en) | 2001-06-28 | 2004-05-18 | Metronic Minimed, Inc. | Methods of evaluating protein formulation stability and surfactant-stabilized insulin formulations derived therefrom |
DE60317365T2 (de) | 2002-11-08 | 2008-08-21 | F. Hoffmann-La Roche Ag | Substituierte 4-alkoxyoxazol derivate als ppar agonisten |
US7264813B2 (en) * | 2003-09-24 | 2007-09-04 | Nikken Sohonsha Corporation | Therapeutic uses of Dunaliella powder |
CN102389427A (zh) * | 2011-10-10 | 2012-03-28 | 成都恒瑞制药有限公司 | 含有罗格列酮和盐酸西替利嗪的固体口服制剂 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE376829T1 (de) * | 1993-09-15 | 2007-11-15 | Daiichi Sankyo Co Ltd | Verwendung von thiazolidindionen zur vorbeugung oder verzögerung des auftretens des nichtinsulinabhängigen diabetes mellitus (niddm) |
WO1997005875A2 (en) * | 1995-08-10 | 1997-02-20 | Warner-Lambert Company | A method of reducing the amount of exogenous insulin administered to a patient having noninsulin-dependent diabetes mellitus |
KR19990045756A (ko) * | 1995-09-18 | 1999-06-25 | 윌리암 엘. 레스페스 | Rxr 작용제를 이용하는 niddm 치료 방법 |
-
1997
- 1997-06-18 GB GBGB9712866.4A patent/GB9712866D0/en active Pending
-
1998
- 1998-06-15 PL PL98343123A patent/PL343123A1/xx unknown
- 1998-06-15 KR KR1019997011864A patent/KR20010013843A/ko not_active Application Discontinuation
- 1998-06-15 IL IL13314398A patent/IL133143A0/xx unknown
- 1998-06-15 AU AU82163/98A patent/AU8216398A/en not_active Abandoned
- 1998-06-15 WO PCT/EP1998/003692 patent/WO1998057636A1/en not_active Application Discontinuation
- 1998-06-15 EA EA200000042A patent/EA004800B1/ru not_active IP Right Cessation
- 1998-06-15 HU HU0003260A patent/HUP0003260A3/hu unknown
- 1998-06-15 EP EP98932169A patent/EP0999837A1/en not_active Withdrawn
- 1998-06-15 ID IDW991627A patent/ID23951A/id unknown
- 1998-06-15 CN CNB988062232A patent/CN1133431C/zh not_active Expired - Fee Related
- 1998-06-15 BR BR9810444-6A patent/BR9810444A/pt not_active IP Right Cessation
- 1998-06-15 AP APAP/P/1999/001718A patent/AP1287A/en active
- 1998-06-15 UA UA99126881A patent/UA70299C2/uk unknown
- 1998-06-15 CA CA002294141A patent/CA2294141A1/en not_active Abandoned
- 1998-06-15 TR TR1999/03095T patent/TR199903095T2/xx unknown
- 1998-06-15 SK SK1793-99A patent/SK179399A3/sk unknown
- 1998-06-15 JP JP50375799A patent/JP2002504138A/ja not_active Ceased
- 1998-06-17 AR ARP980102886A patent/AR015894A1/es not_active Application Discontinuation
- 1998-06-17 AR ARP980102883A patent/AR012997A1/es not_active Application Discontinuation
- 1998-06-17 DZ DZ980131A patent/DZ2521A1/xx active
- 1998-06-17 TW TW087109619A patent/TW587937B/zh not_active IP Right Cessation
- 1998-06-17 MA MA25122A patent/MA26511A1/fr unknown
- 1998-06-17 ZA ZA9805237A patent/ZA985237B/xx unknown
- 1998-06-18 CO CO98034654A patent/CO4940454A1/es unknown
- 1998-06-18 IN IN1698DE1998 patent/IN189723B/en unknown
- 1998-06-18 PE PE1998000535A patent/PE104499A1/es not_active Application Discontinuation
- 1998-06-18 UY UY25050A patent/UY25050A1/es unknown
-
1999
- 1999-12-17 OA OA9900296A patent/OA11517A/en unknown
- 1999-12-17 NO NO996265A patent/NO996265D0/no not_active Application Discontinuation
-
2000
- 2000-01-06 BG BG104059A patent/BG104059A/xx unknown
Non-Patent Citations (1)
Title |
---|
See references of WO9857636A1 * |
Also Published As
Publication number | Publication date |
---|---|
CN1133431C (zh) | 2004-01-07 |
TW587937B (en) | 2004-05-21 |
AR015894A1 (es) | 2001-05-30 |
KR20010013843A (ko) | 2001-02-26 |
IN189723B (no) | 2003-04-19 |
JP2002504138A (ja) | 2002-02-05 |
NO996265L (no) | 1999-12-17 |
WO1998057636A1 (en) | 1998-12-23 |
SK179399A3 (en) | 2000-11-07 |
BG104059A (en) | 2000-10-31 |
HUP0003260A2 (hu) | 2001-05-28 |
ZA985237B (en) | 2000-02-17 |
UY25050A1 (es) | 2000-09-29 |
AU8216398A (en) | 1999-01-04 |
HUP0003260A3 (en) | 2001-12-28 |
TR199903095T2 (xx) | 2000-08-21 |
PL343123A1 (en) | 2001-07-30 |
PE104499A1 (es) | 2000-01-13 |
AR012997A1 (es) | 2000-11-22 |
EA004800B1 (ru) | 2004-08-26 |
ID23951A (id) | 2000-06-08 |
AP9901718A0 (en) | 1999-12-31 |
AP1287A (en) | 2004-06-26 |
OA11517A (en) | 2004-02-04 |
EA200000042A1 (ru) | 2000-08-28 |
CO4940454A1 (es) | 2000-07-24 |
NO996265D0 (no) | 1999-12-17 |
BR9810444A (pt) | 2000-09-05 |
UA70299C2 (en) | 2004-10-15 |
MA26511A1 (fr) | 2004-12-20 |
CN1260715A (zh) | 2000-07-19 |
GB9712866D0 (en) | 1997-08-20 |
DZ2521A1 (fr) | 2003-02-08 |
IL133143A0 (en) | 2001-03-19 |
CA2294141A1 (en) | 1998-12-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0996444B1 (en) | Treatment of diabetes with thiazolidinedione and metformin | |
US20050059706A1 (en) | Treatment of diabetes with thiazolidinedione and metformin | |
US20080058388A1 (en) | Treatment of diabetes with thiazolidinedione and sulphonylurea | |
AP1287A (en) | Treatment of diabetes with rosiglitazone and insulin. | |
EP0999845B1 (en) | Treatment of diabetes with thiazolidinedione and sulphonylurea | |
US20040106543A1 (en) | Treatment of diabetes with rosiglitazone and insulin | |
NZ501345A (en) | 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 | |
WO1999003476A1 (en) | Treatment of diabetes with thiazolidinedione and sulphonylurea | |
AU783539B2 (en) | Treatment of diabetes with thiazolidinedione and sulphonylurea | |
NZ518076A (en) | 5-[4-[2-(N-methyl-N-(2- pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione (BRL49653) for treating non-insulin dependent diabetes (NIDDM) | |
AU778947B2 (en) | Treatment of diabetes with thiazolidinedione and metformin | |
AU1552102A (en) | Treatment of diabetes with rosiglitazone and insulin | |
US20020123514A1 (en) | Treatment of diabetes with thiazolidinedione and alpha-glucosidase inhibitor | |
MXPA99012065A (en) | Treatment of diabetes with rosiglitazone and insulin | |
NZ520542A (en) | Treatment of diabetes with thiazolidinedione and metformin |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 19991119 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE |
|
AX | Request for extension of the european patent |
Free format text: RO PAYMENT 19991119;SI PAYMENT 19991119 |
|
17Q | First examination report despatched |
Effective date: 20011108 |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: SMITHKLINE BEECHAM PLC |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20050514 |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1028198 Country of ref document: HK |