OA11517A - Treatment of diabetes with rosiglitazone and insulin. - Google Patents
Treatment of diabetes with rosiglitazone and insulin. Download PDFInfo
- Publication number
- OA11517A OA11517A OA9900296A OA9900296A OA11517A OA 11517 A OA11517 A OA 11517A OA 9900296 A OA9900296 A OA 9900296A OA 9900296 A OA9900296 A OA 9900296A OA 11517 A OA11517 A OA 11517A
- Authority
- OA
- OAPI
- Prior art keywords
- compound
- insulin
- administration
- pharmaceutically acceptable
- diabètes
- Prior art date
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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
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- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Emergency Medicine (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)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
Abstract
A method for the treatment of diabetes mellitus and conditions associated with diabetes mellitus in a mammal, which method comprises administering an effective non-toxic and pharmaceutically acceptable amount of Compound (I) and insulin to a mammal in need thereof.
Description
1 011 517
NOVEL METHOD OF TREATMENT
This invention relates to a method of treatment, in particular to a method for thetreatment of diabètes mellitus, especially non-insulin dépendent diabètes (NIDDM) or 5 Type II diabètes and conditions associated with diabètes mellitus.
Insulin is a front line treatment agent for Type I diabètes (or Insulin Dépendent Diabètes). It is also used as an antihyperglycaemic agent in the treatmentof NIDDM.
European Patent Application, Publication Number 0,306,228 relates to certain10 thiazolidinedione dérivatives disclosed as having antihyperglycaemic and hypolipidaemic activity. One particular thiazolidinedione disclosed in EP 0306228 is5-[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 sait at example 1 thereof. 15 International Patent Application, publication number WO97/05875 discloses a method for reducing the amount of exogenous insulin administered to a patient havingNIDDM by administering a therapeutically effective amount of a thiazolidinedionedérivative and/or a related compound.
It is now surprisingly indicated that a spécifie amount of Compound (I) in 20 combination with insulin provides a particularly bénéficiai effect on glycaemic control, such combination is therefore particularly useful for the treatment of diabètesmellitus, especially Type Π diabètes and conditions associated with diabètes mellitus.
Accordingly, the invention provides a method for the treatment of diabètesmellitus, especially Type Π diabètes and conditions associated with diabètes mellitus 25 in a mammal such as a human, which method comprises administering an effectivenon-toxic and pharmaceutically acceptable amount of Compound (I) and insulin, to amammal in need thereof.
Preferably, the amount of Compound (I) administered is up to 12 mg,especially when administered per day. 30 The method comprises either co-administration of Compound (I) and insulin or the sequential administration thereof.
Co-administration includes administration of a formulation whichincludes both an insulin sensitiser, such as Compound (I), and insulin or, moresuitably, the essentially simultaneous administration of separate formulations of each 35 agent.
In one particular aspect, the method comprises the administration of 2 to 12 mg of Compound (I), especially when administered per day. 2 011517
Particularly, the method comprises the administration of 2 to 4,4 to 8 or 8 to12 mg of Compound (I) per day.
Particularly, the method comprises the administration of 2 to 4mg ofCompound (I), especially when administered per day. 5 Particularly, 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 whenadministered per day.
Particularly, the method comprises the administration of 8 to 12 mg ofCompound (I), especially when administered per day. 10 Preferably, the method comprises the administration of 2 mg of Compound (I), especially when administered per day.
Preferably, the method comprises the administration of 4 mg of Compound(I), especially when administered per day.
Preferably, the method comprises the administration of 8 mg of Compound 15 (I), especially when administered per day.
It will be understood that Compound (I) and the insulin are each administered in a pharmaceutically acceptable form, including for Compound (I), pharmaceuticallyacceptable dérivatives such as pharmaceutically acceptable salts and solvatés thereof.
Suitable pharmaceutically acceptable salted forms of Compound (I) include 20 those described in EP 0306228 and WO94/05659. A preferred pharmaceuticallyacceptable sait 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 25 standard reference texts such as the British and US Pharmacopoeias, Remington'sPharmaceutical Sciences (Mack Publishing Co.) and Martindale The ExtraPharmacopoeia (London, The Pharmaceutical Press) (for example see the 31 st Editionpage 341 and pages cited therein).
Compound (I) or, a pharmaceutically acceptable sait thereof, or a 30 pharmaceutically acceptable solvaté thereof, may be prepared using known methods,for example those disclosed in EP 0306228 and WO94/05659. The disclosures of EP0306228 and WO94/05659 are incorporated herein by reference.
Compound (I) may exist in one of several tautomeric forms, ail of which are encompassed by the term Compound (I) as individual tautomeric forms or as mixtures 35 thereof. Compound (I) contains a chiral carbon atom, and hence can exist in one or more stereoisomeric forms, the term Compound (I) encompasses ail of these isomeric forms whether as individual isomers or as mixtures of isomers, including racemates. 3 011517
Insulin is prepared according to known methods, such methods are found orare referred to in standard reference texts, such as the British and US Pharmacopoeias,Remington's Pharmaceutical Sciences (Mack Publishing Co.) and Martindale TheExtra Pharmacopoeia (London, The Pharmaceutical Press) (for example see the 3 lst 5 Edition page 341 and pages cited therein).
When used herein the term 'conditions associated with diabètes' includesconditions associated with diabètes mellitus itself and complications associated withdiabètes mellitus. 'Conditions associated with diabètes mellitus itself include hyperglycaemia, 10 insulin résistance, including acquired insulin résistance and obesity. Further conditions associated with diabètes mellitus itself include hypertension andcardiovascular disease, especially atherosclerosis and conditions associated withinsulin résistance. Conditions associated with insulin résistance include polycysticovarian syndrome and steroid induced insulin résistance and gestational diabètes. 15 'Complications associated with diabètes mellitus' includes rénal disease, especially rénal disease associated with Type Π diabètes, neuropathy and retinopathy. Rénal diseases associated with Type II diabètes include nephropathy,glomerulonephritis, glomerular sclerosis, nephrotic syndrome, hypertensivenephrosclerosis and end stage rénal disease. 20 As used herein the term 'pharmaceutically acceptable' embraces both human and veterinary use: for example the term 'pharmaceutically acceptable' embraces aveterinarily acceptable compound.
For the avoidance of doubt, when reference is made herein to scalar amounts,including mg amounts, of Compound (I) in a pharmaceutically acceptable form, the 25 scalar amount referred to is made in respect of Compound (I) per se·. For example 2mg of Compound (I) in the form of the maleate sait is that amount of maleate saitwhich contains 2 mg of Compound (I).
Diabètes mellitus is preferably Type Π diabètes.
The particularly bénéficiai effect on glycaemic control provided by the 30 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, forexample by measurement of a typically used index of glycaemic control such asfasting plasma glucose or glycosylated haemoglobin (Hb Aie). Such indices are 35 determined using standard methodology, for example those described in: Tuescher A,Richterich, P., Schweiz. med. Wschr. 101 (1971), 345 and 390 and Frank P.,'Monitoring the Diabetic Patent with Glycosolated Hemoglobin Measurements',Clinical Products 1988 4 011517
In a preferred aspect, the dosage level of each of the active agents when usedin accordance with the treatment of the invention will be less than would hâve beenrequired from a purely additive effect upon glycaemic control.
In the method of the invention, the active médicaments are preferably5 administered in pharmaceutical composition form. As indicated above, such compositions can include both médicaments or one only of the médicaments.
In the treatment of the invention, insulin is usually administered by injection or by other known methods, for example those described in the reference textsmentioned herein. Thus the following comments relating to compositions, 10 formulations and methods of administration suitably refer to the compositions,formulations and administration of Compound (I).
Usually the compositions are adapted for oral administration. However, theymay be adapted for other modes of administration, for example parentéraladministration, sublingual or transdermal administration. 15 The compositions may be in the form of tablets, capsules, powders, granules, lozenges, suppositories, reconstitutable powders, or liquid préparations, such as oralor stérile parentéral solutions or suspensions.
In order to obtain consistency of administration it is preferred that acomposition of the invention is in the form of a unit dose. 20 Unit dose présentation forms for oral administration may be tablets and capsules and may contain conventional excipients such as binding agents, for examplesyrup, acacia, gelatin, sorbitol, tragacanth, or polyvinylpyrrolidone; fillers, forexample lactose, sugar, maize-starch, calcium phosphate, sorbitol or glycine;tabletting lubricants, for example magnésium stéarate; disintegrants, for example 25 starch, polyvinylpyrrolidone, sodium starch glycollate or microcrystalline cellulose;or pharmaceutically acceptable wetting agents such as sodium lauryl sulphate.
The solid oral compositions may be prepared by conventional methods ofblending, filling or tabletting. Repeated blending operations may be used to distributethe active agent throughout those compositions employing large quantities of fillers. 30 Such operations are of course conventional in the art. The tablets may be coatedaccording to methods well known in normal pharmaceutical practice, in particularwith an enteric coating.
Oral liquid préparations may be in the form of, for example, émulsions,syrups, or élixirs, or may be presented as a dry product for reconstitution with water 35 or other suitable vehicle before use. Such liquid préparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methylcellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminium stéarategel, hydrogenated edible fats; emulsifying agents, for example lecithin, sorbitan 5 011517 monooleate, or acacia; non-aqueous vehicles (which may include edible oils), forexample almond oil, fractionated coconut oil, oily esters such as esters of glycérine,propylene glycol, or ethyl alcohol; preservatives, for example methyl or propylp-hydroxybenzoate or sorbic acid; and if desired conventional flavouring or colouring 5 agents.
For parentéral administration, fluid unit dosage forms are prepared utilizingthe compound and a stérile vehicle, and, depending on the concentration used, can beeither suspended or dissolved in the vehicle. In preparing solutions the compound canbe dissolved in water for injection and filter sterilized before filling into a suitable vial 10 or ampoule and sealing. Advantageously, adjuvants such as a local anaesthetic, apreservative and buffering agents can be dissolved in the vehicle. To enhance thestability, the composition can be frozen after filling into the vial and the waterremoved under vacuum. Parentéral suspensions are prepared in substantially the samemanner, except that the Compound (I)s suspended in the vehicle instead of being 15 dissolved, and sterilization cannot be accomplished by filtration. The compound canbe sterilized by exposure to ethylene oxide before suspending in the stérile vehicle.Advantageously, a surfactant or wetting agent is included in the composition tofacilitate uniform distribution of the compound.
Compositions may contain from 0.1% to 99% by weight, preferably from 20 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 bywritten or printed instructions for use.
The compositions are formulated according to conventional methods, such as 25 those disclosed herein and in standard reference texts, for example the British and USPharmacopoeias, Remington's Pharmaceutical Sciences (Mack Publishing Co.) andMartindale The Extra Pharmacopoeia (London The Pharmaceutical Press) (forexample see the 31 st Edition page 341 and pages cited therein) and Harry'sCosmeticology (Leonard Hill Books). 30 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).
In the treatments the two médicaments may be administered from 1 to 6 35 times a day, but most preferably 1 or 2 times per day.
Suitable dosages of insulin, including unit dosages, 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 6 011517
Extra Pharmacopoeia (London, The Pharmaceutical Press) (for example see the 31 stEdition 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. 5 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, 8.4to 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 to12mg. 10 No adverse toxicological effects hâve been established for the compositions or methods of the invention in the abovementioned dosage ranges.
The following example illustrâtes the invention but does not limit it in any way. 7 011517
COMPOUND (I) COMPOSITIONS A Concentrate Préparation 5 Approximately two thirds of the lactose monohydrate is passed through a suitablescreen and blended with the milled maleate sait of Compound (I).
Sodium starch glycollate, hydoxypropyl methylcellulose, microcrystallinecellulose and the remaining lactose are passed through a suitable screen and addedto the mixture. Blending is then continued. The resulting mixture is then wet 10 granulated with purified water. The wet granules are then screened, dried on afluid bed drier and the dried granules are passed through a further screen andfinally homogenised.
% COMPOSITION OF GRANULAR CONCENTRATE 15
Ingrédient Quantity (%) Milled Compound (I) as maleatesait 13.25 (puremaleate sait) Sodium Starch Glycollate 5.00 Hydoxypropyl Methylcellulose2910 5.00 Microcrystalline Cellulose 20.0 Lactose Monohydrate, regulargrade to 100 Purified water ♦ * Removed during processing. 20 8 011517 B Formulation of the concentrate into tablets.
The granules from above are placed into a tumble blender. Approximately twothirds of the lactose is screened and added to the blender. The microcrystalline 5 cellulose, sodium starch glycollate, magnésium stéarate and remaining lactose arescreened and added to the blender and the mixture blended together. Theresulting mix is then compressed on a rotary tablet press to a target weight of150mg for the 1,2 and 4mg tablets and to a target weight of 300mg for the 8mgtablets. 10 The tablet cores are then transferred to a tablet coating machine, pre-warmed with warm air (approximately 65°C) and film coated until the tabletweight has increased by 2.0% to 3.5%.
Quantity (mg per Tablet)
Tablet Strength l.Omg 2.0mg 4.0mg 8.0mg Active Ingrédient: Compound (I) maleate Concentrate granules 10.00 20.00 40.00 80.00 Other Ingrédients: - Sodium Starch Glycollate 6.96 6.46 5.46 10.92 Microcrystalline Cellulose 27.85 25.85 21.85 43.70 Lactose monohydrate 104.44 96.94 81.94 163.88 Magnésium Stéarate 0.75 0.75 0.75 1.50 Total Weight of Tablet Core 150.0 150.0 150.0 300.0 Aqueous film coating material 4.5 4.5 4.5 9.0 Total Weight of Film Coated Tablet 154.5 154.5 154.5 309.0 15
Claims (15)
1. A method for the treatment of diabètes mellitus and conditions associatedwith diabètes mellitus in a mammal, which method comprises administering an 5 effective non-toxic and pharmaceutically acceptable amount of Compound (I)and insulin, to a mammal in need thereof.
2. A method according to claim 1, which comprises the administration of upto 12 mg of Compound (I). 10
3. A method according to claim 1 or claim 2, which comprises theadministration of 2 to 12 mg of Compound (I).
4. A method according to any one of claims 1 to 3, which comprises the 15 administration of 2 to 4,4 to 8 or 8 to 12 mg of Compound (I).
5. A method according to any one of claims 1 to 3, which comprises theadministration of 2 to 4mg of Compound (I). 20
6. A method according to any one of claims 1 to 3, which comprises the administration of 4 to 8mg of Compound (I).
7. A method according to any one of claims 1 to 3, which comprises theadministration of 8 to 12 mg of Compound (I). 25
8. A method according to any one of claims 1 to 3, which comprises theadministration of 2 mg of Compound (I).
9. A method according to any one of claims 1 to 3, which comprises the30 administration of 4 mg of Compound (I).
9 011517 Claims
10. A method according to any one of claims 1 to 3, which comprises theadministration of 8 mg of Compound (I). 10 011517
11. A pharmaceutical composition comprising Compound (I), insulin and apharmaceutically acceptable carrier therefor.
12. A composition according to claim 11, wherein the insulin sensitiser is 5 Compound (I)
13. A composition according to claim 11 or claim 12, which comprises up to12 mg or 2 to 12 mg of Compound (I). 10
14. A pharmaceutical composition comprising Compound (I), insulin and a pharmaceutically acceptable carrier therefor, for use as an active therapeuticsubstance.
15. A pharmaceutical composition comprising Compound (I), insulin and a 15 pharmaceutically acceptable carrier therefor, for use in the treatment ofdiabètes mellitus and conditions associated with diabètes mellitus.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9712866.4A GB9712866D0 (en) | 1997-06-18 | 1997-06-18 | Novel method of treatment |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA11517A true OA11517A (en) | 2004-02-04 |
Family
ID=10814527
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| OA9900296A OA11517A (en) | 1997-06-18 | 1999-12-17 | Treatment of diabetes with rosiglitazone and insulin. |
Country Status (30)
| Country | Link |
|---|---|
| EP (1) | EP0999837A1 (en) |
| JP (1) | JP2002504138A (en) |
| KR (1) | KR20010013843A (en) |
| CN (1) | CN1133431C (en) |
| AP (1) | AP1287A (en) |
| AR (2) | AR012997A1 (en) |
| AU (1) | AU8216398A (en) |
| BG (1) | BG104059A (en) |
| BR (1) | BR9810444A (en) |
| CA (1) | CA2294141A1 (en) |
| CO (1) | CO4940454A1 (en) |
| DZ (1) | DZ2521A1 (en) |
| EA (1) | EA004800B1 (en) |
| GB (1) | GB9712866D0 (en) |
| HU (1) | HUP0003260A3 (en) |
| ID (1) | ID23951A (en) |
| IL (1) | IL133143A0 (en) |
| IN (1) | IN189723B (en) |
| MA (1) | MA26511A1 (en) |
| NO (1) | NO996265D0 (en) |
| OA (1) | OA11517A (en) |
| PE (1) | PE104499A1 (en) |
| PL (1) | PL343123A1 (en) |
| SK (1) | SK179399A3 (en) |
| TR (1) | TR199903095T2 (en) |
| TW (1) | TW587937B (en) |
| UA (1) | UA70299C2 (en) |
| UY (1) | UY25050A1 (en) |
| WO (1) | WO1998057636A1 (en) |
| ZA (1) | ZA985237B (en) |
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 |
| KR100744359B1 (en) | 1999-04-23 | 2007-07-30 | 스미스클라인비이참피이엘시이 | Thiazolidinedione Derivative and its Use as Antidiabetic |
| 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 |
| AU5760900A (en) | 1999-06-25 | 2001-01-31 | 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 |
| WO2002100396A1 (en) * | 2001-06-07 | 2002-12-19 | 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 |
| CN1711084B (en) * | 2002-11-08 | 2010-04-28 | 霍夫曼-拉罗奇有限公司 | Substituted 4-alkoxyoxazol derivatives as PPAR agonists |
| US7264813B2 (en) | 2003-09-24 | 2007-09-04 | Nikken Sohonsha Corporation | Therapeutic uses of Dunaliella powder |
| CN102389427A (en) * | 2011-10-10 | 2012-03-28 | 成都恒瑞制药有限公司 | Solid oral preparation containing rosiglitazone and cetirizine hydrochloride |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE376829T1 (en) * | 1993-09-15 | 2007-11-15 | Daiichi Sankyo Co Ltd | USE OF THIAZOLIDINDIONES TO PREVENT OR DELAY THE OCCURMENT OF NONINSULIN DEPENDENT DIABETES MELLITUS (NIDDM) |
| KR19990036290A (en) * | 1995-08-10 | 1999-05-25 | 로즈 암스트롱 | Reduction of Exogenous Insulin Dosage in Non-insulin-Dependent Diabetic Patients |
| EP0859608B1 (en) * | 1995-09-18 | 2004-02-11 | Ligand Pharmaceuticals, Inc. | Treating niddm with rxr agonists |
-
1997
- 1997-06-18 GB GBGB9712866.4A patent/GB9712866D0/en active Pending
-
1998
- 1998-06-15 EA EA200000042A patent/EA004800B1/en not_active IP Right Cessation
- 1998-06-15 WO PCT/EP1998/003692 patent/WO1998057636A1/en not_active Application Discontinuation
- 1998-06-15 CA CA002294141A patent/CA2294141A1/en not_active Abandoned
- 1998-06-15 BR BR9810444-6A patent/BR9810444A/en not_active IP Right Cessation
- 1998-06-15 IL IL13314398A patent/IL133143A0/en unknown
- 1998-06-15 TR TR1999/03095T patent/TR199903095T2/en unknown
- 1998-06-15 UA UA99126881A patent/UA70299C2/en unknown
- 1998-06-15 KR KR1019997011864A patent/KR20010013843A/en not_active Application Discontinuation
- 1998-06-15 JP JP50375799A patent/JP2002504138A/en not_active Ceased
- 1998-06-15 CN CNB988062232A patent/CN1133431C/en not_active Expired - Fee Related
- 1998-06-15 AU AU82163/98A patent/AU8216398A/en not_active Abandoned
- 1998-06-15 HU HU0003260A patent/HUP0003260A3/en unknown
- 1998-06-15 AP APAP/P/1999/001718A patent/AP1287A/en active
- 1998-06-15 ID IDW991627A patent/ID23951A/en unknown
- 1998-06-15 PL PL98343123A patent/PL343123A1/en unknown
- 1998-06-15 SK SK1793-99A patent/SK179399A3/en unknown
- 1998-06-15 EP EP98932169A patent/EP0999837A1/en not_active Withdrawn
- 1998-06-17 DZ DZ980131A patent/DZ2521A1/en active
- 1998-06-17 ZA ZA9805237A patent/ZA985237B/en unknown
- 1998-06-17 MA MA25122A patent/MA26511A1/en unknown
- 1998-06-17 AR ARP980102883A patent/AR012997A1/en not_active Application Discontinuation
- 1998-06-17 AR ARP980102886A patent/AR015894A1/en not_active Application Discontinuation
- 1998-06-17 TW TW087109619A patent/TW587937B/en not_active IP Right Cessation
- 1998-06-18 UY UY25050A patent/UY25050A1/en unknown
- 1998-06-18 CO CO98034654A patent/CO4940454A1/en unknown
- 1998-06-18 PE PE1998000535A patent/PE104499A1/en not_active Application Discontinuation
- 1998-06-18 IN IN1698DE1998 patent/IN189723B/en unknown
-
1999
- 1999-12-17 OA OA9900296A patent/OA11517A/en unknown
- 1999-12-17 NO NO996265A patent/NO996265D0/en not_active Application Discontinuation
-
2000
- 2000-01-06 BG BG104059A patent/BG104059A/en unknown
Also Published As
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|---|---|
| IN189723B (en) | 2003-04-19 |
| EP0999837A1 (en) | 2000-05-17 |
| HUP0003260A2 (en) | 2001-05-28 |
| IL133143A0 (en) | 2001-03-19 |
| NO996265L (en) | 1999-12-17 |
| UY25050A1 (en) | 2000-09-29 |
| CA2294141A1 (en) | 1998-12-23 |
| AR015894A1 (en) | 2001-05-30 |
| EA200000042A1 (en) | 2000-08-28 |
| AU8216398A (en) | 1999-01-04 |
| CN1133431C (en) | 2004-01-07 |
| PL343123A1 (en) | 2001-07-30 |
| AR012997A1 (en) | 2000-11-22 |
| TR199903095T2 (en) | 2000-08-21 |
| PE104499A1 (en) | 2000-01-13 |
| GB9712866D0 (en) | 1997-08-20 |
| CN1260715A (en) | 2000-07-19 |
| BG104059A (en) | 2000-10-31 |
| SK179399A3 (en) | 2000-11-07 |
| BR9810444A (en) | 2000-09-05 |
| EA004800B1 (en) | 2004-08-26 |
| NO996265D0 (en) | 1999-12-17 |
| ZA985237B (en) | 2000-02-17 |
| MA26511A1 (en) | 2004-12-20 |
| CO4940454A1 (en) | 2000-07-24 |
| HUP0003260A3 (en) | 2001-12-28 |
| UA70299C2 (en) | 2004-10-15 |
| KR20010013843A (en) | 2001-02-26 |
| TW587937B (en) | 2004-05-21 |
| JP2002504138A (en) | 2002-02-05 |
| ID23951A (en) | 2000-06-08 |
| AP9901718A0 (en) | 1999-12-31 |
| AP1287A (en) | 2004-06-26 |
| WO1998057636A1 (en) | 1998-12-23 |
| DZ2521A1 (en) | 2003-02-08 |
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