AP1223A - Use of thiazolidinediones for the treatment of hyperglycaemia. - Google Patents

Use of thiazolidinediones for the treatment of hyperglycaemia. Download PDF

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Publication number
AP1223A
AP1223A APAP/P/2000/001788A AP2000001788A AP1223A AP 1223 A AP1223 A AP 1223A AP 2000001788 A AP2000001788 A AP 2000001788A AP 1223 A AP1223 A AP 1223A
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insulin sensitiser
glucose levels
insulin
range
hyperglycaemia
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APAP/P/2000/001788A
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AP2000001788A0 (en
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Robin Edwin Buckingham
Stephen Alistair Smith
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Smithkline Beecham Plc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Emergency Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

A method for the treatment of hyperglycaemia wherein plasma levels in the range of from bigger than/126mg/dl to 140 mg/dl, which method comprises administering an effective nontoxic and pharmaceutically acceptable amount of an insulin sensitiser, to a mammal in need thereof.

Description

USE OF THIAZOLIDINEDIONES FOR THE TREATMENT OF HYPERGLYCAEMIA
This invention relates to a method of treatment, in particular to a method for the treatment of a certain, specified hyperglycaemia.
European Patent Application, Publication Number 0,306,228 relates to certain thiazolidinedione derivatives disclosed as having hypoglycaemic and hypolipidaemic activity. One particular thiazolidinedione disclosed in EP 0306228 is 5-[4~{2-(N-methylN-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione (hereinafter 'Compound (I)'). WO94/05659 discloses certain salts of Compound (I) including the maleate salt.
Compound (I) is an example of a class of anti-hyperglycaemic agents known as 'insulin sensitisers’. In particular Compound (I) is a thiazolidinedione insulin sensitiser.
European Patent Applications, Publication Numbers; 0008203, 0139421,
0032128, 0428312, 0489663, 0155845, 0257781, 0208420, 0177353, 0319189, 0332331. 0332332, 0528734, 0508740; International Patent Application, Publication Numbers
92/18501, 93/02079, 93/22445 and United States Patent Numbers 5104888 and 5478852, also disclose certain thiazolidinedione insulin sensitisers.
.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 W094/01420. 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 Application, Publication Number 0533933, Japanese Patent Application Publication
Number 05271204 and United States Patent Number 5264451.
The Report of the Expert Committee of the Diagnosis and Classification of
Diabetes Meilitus (Diabetes Care, vol 20(7), 1997, 1183-1197) states that Type 2 diabetes is characterised by fasting plasma glucose levels of > 126mg/dl (where fasting is defined
J as no calorific intake for at least 8 hours). It is also described therein how the development of diabetes commonly occurs over a period of several years characterised by a rise in fasting serum glycaemia levels from levels generally considered to be normal plasma glucose levels of approximately 1 lOmg/dl - through to the stated hypergiycaemia characteristic of frank Type 2 diabetes. The Report also refers to metabolic stages intermediate between normal glucose homeostasis and diabetes, including impaired glucose tolerance and impaired fasting glucose.
It is known from EP03 06228 that Compound I is useful in the prophylaxis of hypergiycaemia and hence for the treatment of impaired glucose tolerance. International
Patent Application, Publication number WO 95/07694 also discloses that
-188/10/00 td/dV thiazolidinediones can be used to treat impaired glucose tolerance to prevent or delay the onset of Type 2 diabetes mellitus. However, EP0306228 and WO 95/07694 do not disclose the treatment of any particular range of glycaemias.
It is now surprisingly indicated that Compound (I) provides a particularly 5 beneficial effect on glycaemic control in the range of hyperglycaemia from >126mg/dl to
140mg/dl, thereby delaying or preventing further elevation of the hypergylcaemia.
Accordingly, the invention provides a method for the treatment of hyperglycaemia, especially fasting hyperglycaemia, wherein plasma glucose levels are in the range of from >126mg/dl to 140mg/dl, which method comprises administering an effective non-toxic and pharmaceutically acceptable amount of an insulin sensitiser, to a mammal in need thereof.
In a further aspect the invention provides a method for improving glycaemic control in conditions characterised by hyperglycaemia, especially fasting hyperglycaemias, wherein the improvement is provided wherein plasma glucose ievels are in the range of from >126mg/dl to 140mg/dl, thereby delaying or preventing further elevation of the hypergylcaemia, which method comprises administering an effective non-toxic and pharmaceutically acceptable amount of an insulin sensitiser, to a mammal in need thereof.
In yet a further aspect, the invention provides a method for the prophylaxis of hyperglycaemia, especially fasting hyperglycaemia, wherein plasma glucose levels are >140mg/dl, which method comprises administering an effective non-toxic and pharmaceutically acceptable amount of an insulin sensitiser, to a mammal in need thereof.
One particular group of conditions defined herein, in addition to being characterised by hyperglycaemia wherein fasting plasma glucose levels are in the range of from >126mg/dl to 140me/dl are further characterised by hyperglvcaemia wherein plasma glucose levels following an oral glucose tolerance test are <140mg/dl.
A further group of conditions defined herein are those wherein in addition to being characterised by hyperglycaemia wherein fasting plasma glucose levels are in the range of from >126mg/dl to 140mg/dl, are further characterised by hyperglycaemias wherein plasma glucose levels following an oral glucose tolerance test are in the range of from 140 to <200 mg/di.
Suitably the hyperglycaemia is that associated with the Type 2 diabetes mellitus syndrome.
A suitable insulin sensitiser is a thiazolidinedione insulin sensitiser.
A suitable thiazolidinedione insulin sensitiser is Compound (I).
Other suitable thiazolidinedione insulin sensitisers include (+) -5-((4-((3.4dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-l-benzopyran-2-yl)methoxy]phenyl]methyl]2.4-thiazoiidinedione (or troglitazone), 5-(4-(( l-methylcvclohexyl)methoxy]benzyl]
-2CO
CD **··
001223 thiazolidine-2,4-dione (or ciglitazone), 5-[4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyi] thiazoiidine-2,4-dione (or piogiitazone) or 5-[(2-benzyl-2,3-dihydrobenzopyran)-5vlmethyl)thiazolidine-2,4-dione (or englitazone)
In one particular aspect, the method comprises the administration of 2 to 12 mg of Compound (I), especially when administered per day.
Particularly, the method comprises the administration of 2 to 4,4 to 8 or 8 to 12 mg of Compound (I) per day.
Particularly, the method comprises the administration of 2 to 4mg of Compound (I), especially when administered per day.
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 w'hen administered per day.
Particularly, the method comprises the administration of 8 to 12 mg of Compound (I), especially when administered per day.
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 (I), especially when administered per day.
It will be understood that the insulin sensitiser, such as compound (I) is administered in a pharmaceutically acceptable form, including pharmaceutically acceptable derivatives such as pharmaceutically acceptable salts, esters and solvates thereof, as appropriate.
Suitable pharmaceutically acceptable salted forms of the insulin sensitisers, such as Compound (I), include those described in the above mentioned patents and patent applications such as in EP 0306228 and WO94/05659 for Compound (I).
A preferred pharmaceutically acceptable salt for Compound (I) is a maleate. Suitable pharmaceutically acceptable solvated forms of the insulin sensitisers, such as Compound (I), include those described in the above mentioned pr.cr.ts and patent applications, such as in EP 0306228 and WO94/05659 for Compound (I), in particular hydrates.
The thiazolidinedione insulin sensitisers, such as Compound (I), may exist in one of several tautomeric forms, all of which are encompassed herein either as individual tautomeric forms or as mixtures thereof. Certain ofthe insulin sensitisers, such as
Compound (I), contain one or more chiral carbon atom, and hence can exist in two or more stereoisomeric forms: All such forms are encompassed herein w'hether as individual isomers or as mixtures of isomers, including racemates.
-388x10/00 iC/dM
As used herein the term 'pharmaceutically acceptable' embraces both human and veterinary use: tor example the term pharmaceutically acceptable’ embraces a veterinarily acceptable compound.
As used herein the oral glucose tolerance test is that referenced in Diabetes Care 5 1997. vol 20(7), 1183-1197.
.As used herein 'elevated normal' hyperglycaemia is to be taken as generally understood in the art, with reference for example to the Report of the Expen Committee of the Diagnosis and Classification of Diabetes Mellitus but is usually taken to mean glycaemias wherein plasma glucose levels are >1 lOmg/dl.
Suitably, plasma glucose levels are fasting plasma glucose levels.
In the method of the invention, the active medicaments are preferably administered in pharmaceutical composition form. As indicated above, such compositions can include both medicaments or one only of the medicaments.
Such compositions may be prepared by admixing an insulin sensitiser, such as 15 Compound (I) and especially 2 to 12 mg thereof, and a pharmaceutically acceptable carrier therefor.
Usually the 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, .ozenges, suppositories, reconstitutable powders, or liquid preparations, such as oral or sterile parenteral solutions or suspensions.
In order to obtain consistency of administration it is preferred that 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, rnaize-starch, calcium phosphate, sorbitol or glycine; tabletting lubricants, for j example magnesium stearate; disintegrants, for example starch, polyvinylpyrrolidone, sodium starch glycollate or microcrystaliine 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 for the insulin sensitisers include those disclosed in the above mentioned patents and patent applications.
Suitable dosages, including unit dosages, of Compound (I) comprise 1. 2, 3, 4, 5,
6, 7, 8, 9, 10, 11 or 12 mg of Compound (I).
AP/?/ 00/0 1/ 83
-4ΑΡ ο ο 12 2 3
In the treatment the medicaments may be administered from 1 to 6 times a day, but most preferably 1 or 2 times per day.
In the treatment involving compounds other than Compound (I), the required dosages and formulations are generally as described in the above mentioned patent publications which as stated above are incorporated by reference herein: An example includes the administration of 200-800mg of Troglitazone, for example 200. 300 or 400mg.
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.
For parenteral administration, 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. In preparing solutions the compound can be dissolved in water for injection and filter sterilized before filling into a suitable vial or ampoule and sealing. Advantageously, adjuvants such as a local anaesthetic, a preservative and buffering agents can be dissolved in the vehicle. To enhance the stability, 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 medicament is 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. Advantageously, 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.
-5AP ο Ο 1 2 2 3
The composition may, if desired, be in the form of a pack accompanied by written or printed instructions for use.
The compositions are prepared and formulated according to conventional methods, such as those disclosed in standard reference texts, for example the British and
US Pharmacopoeias, Remington's Pharmaceutical Sciences (Mack Publishing Co.), Martindaie The Extra Pharmacopoeia (London, The Pharmaceutical Press) and Harry’s Cosmeticology (Leonard Hill Books).
The invention also provides the use of an insulin sensitiser, such as Compound (I) and especially 2 tc 12 mg thereof, for the manufacture of a medicament for the treatment of hyperglycaemia, especially fasting hyperglycaemia, wherein plasma glucose levels are in the range of from >126mg/dl to 140mg/'dl.
In addition, the invention also provides the use of an insulin sensitiser, such as Compound (I) and especially 2 to 12 mg thereof, for the manufacture of a medicament for improving glycaemic control in conditions characterised by hyperglycaemia, especially fasting hypergiycaemia, the improvement being provided wherein plasma glucose levels are in the range of from >126mg/dl to 140mg/dl, thereby delaying or preventing further elevation of the hypergylcaemia.
In yet a further aspect, the invention provides the use of an insulin sensitiser, such as Compound (I) and especially 2 to 12 mg thereof, for the manufacture of a medicament for the prophylaxis of hypergiycaemia, especially fasting hypergiycaemia, wherein piasma glucose levels are >140mg/dl.
The present invention also provides a pharmaceutical composition comprising an insulin sensitiser, such as Compound (I) and especially 2 to 12 mg thereof, and a pharmaceutically acceptable carrier therefor, for use in the treatment of hypergiycaemia, especially fasting hypergiycaemia, wherein plasma glucose levels are in the range of from > 126mg/dl to 140mg/dl or for the improvement of glycaemic control in conditions characterised by fasting hypergiycaemia, the improvement being provided in the range cf hypergiycaemia wherein plasma glucose levels are in the range of from >126mg/dl to i40mg/dl, thereby delaying or preventing further elevation of the hypergylcaemia or for ihe prophylaxis of hypergiycaemia, especially fasting hypergiycaemia, wherein piasma glucose levels are >140mg/dl.
No adverse toxicological effects are expected for the compositions or methods of the invention in the above mentioned dosage ranges.

Claims (12)

  1. Cl aims s .1 - The use of an insulin sensitiser for the manufacture of a medicament for the treatment of hyperg1ycaemia« b. administering an effective non-toxic and pharmaceutical ly acceptable amount thereof to a mammal •in need, wherein plasms glucose levels are in the range of from >126mg/dl to 140mg/d1.
  2. 2- The? use of an insulin sensitiser according to claim .1, wherein the hyperglyesemia is fasting hyperglycaemia.
  3. 3, The use of an insulin sensitiser according to claim 2, wherein the hyperglycaemia is characterised by fasting plasma glucose levels in the range of from >126mg/dl to 140mg/dl and is further characterised by hyperglycaemia wherein the· plasma glucose levels following an oral glucose tolerance test are <140mg/dl.
  4. 4.. The use of an insulin sensitiser according to claim 2. wherein the hyperglycaemia its characterised by fasting plasma glucose levels .in the range of from ;>.126mg/dl to 14Omg/dl, and is further characterised by hyperg1ycaemias wherein plasma glucose levels following an oral glucose tolerance test are in the range of from .140 to <2OOmg/dl
  5. 5. The use of an insulin sensitiser according to any one of claims 1 to 4, wherein the insulin sensitiser is a t.hi a2 ο 1 id inedione insu 1 i n sensi ti ser .
    A, The use of an insulin sensitiser according to any one of claims 1 to 5, wherein the insulin sensitiser is Compound CI}.
    The use of an wherein 2 to day „
    88 410/00. „4V insulin sensitiser according to claim ό, 12mg of Compound (I) is administered per
    Q, The use of an insulin sensitiser according to any one of claims 1 to 4, wherein the insulin sensitiser is selected from the list. consisting of: ( + )-5- [ [4-· [ (3,4-dihydro-
  6. 6-hydroxy-2,5,
  7. 7 ,
  8. 8-tetramet hyl -2H-I-bensopyran2-y 1) methoxyjpheny3methy3-2?4-thiazo1idinedione (or trog 1 itasone) , 5-C4-C (1 --methy 1 eye 1 ohexy 1 ) m e t h o :·; y 3 benz y 1 3 t hi i a ζ. ο 1 i d i n e - 2 , 4 - d i on e (o r c i g 1 i t a ζ o ne) , 5~C4- E2- ( 5-ethy 1 pyridin-2~y 1 ) ethoxy 3 benzy I 3 thiacol idine— 2,4-dione (or pioglitazone) and 5-£(2-~ benzyl -2,3-dihydrobenzopyrar») -5-yl me thy 1 ) thi is col id ine2,4-dione (or englitazone); or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof,, or a ρharmaceuti ca 11 y a,ccept a b 1 e so 1 vate thereof .
    APOΟ 1223
  9. 9. The use of an insulin sensitiser according to any one of claims .1 to 8, wherein the insulin sensi tiser is .in the 'form of a compositions adapted for oral a d m .1 n i s t r & t i on .
  10. 10. The use of an insulin sensitiser according to claim 9, wherein the composition is; in unit dosage form.
  11. 11. The use of an insulin sensitiser for the manufacture of a medic Ci merit for the treatment of hyperglycsemia wherein plasuna glucose levels are in the range of from > 126mg /d 1 to 140rog / ci 1 .
  12. .12. ft pharmaceutical composition comprising an insulin sensitiser and a pharmaceutically acceptable carrier, for use in the treatment of hyperglycsemia wherein plasma glucose levels in the range of from >126mg/dl to I40mg/dl.
APAP/P/2000/001788A 1997-10-13 1998-10-12 Use of thiazolidinediones for the treatment of hyperglycaemia. AP1223A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9721692.3A GB9721692D0 (en) 1997-10-13 1997-10-13 Novel treatment
PCT/GB1998/003067 WO1999018944A1 (en) 1997-10-13 1998-10-12 Use of thiazolidinediones for the treatment of hyperglycaemia

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AP2000001788A0 AP2000001788A0 (en) 2000-06-30
AP1223A true AP1223A (en) 2003-11-13

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US7045519B2 (en) 1998-06-19 2006-05-16 Chiron Corporation Inhibitors of glycogen synthase kinase 3
KR20010079551A (en) * 1998-07-21 2001-08-22 피터 기딩스 Use Of Glucose Uptake Enhancer for Reducing Apoptosis

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994005659A1 (en) * 1992-09-05 1994-03-17 Smithkline Beecham Plc Substituted thiazolidinedione derivatives
US5478852A (en) * 1993-09-15 1995-12-26 Sankyo Company, Limited Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of impaired glucose tolerance in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus

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* Cited by examiner, † Cited by third party
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EP0842925A1 (en) * 1987-09-04 1998-05-20 Beecham Group Plc Substituted thiazolidinedione derivatives

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994005659A1 (en) * 1992-09-05 1994-03-17 Smithkline Beecham Plc Substituted thiazolidinedione derivatives
US5478852A (en) * 1993-09-15 1995-12-26 Sankyo Company, Limited Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of impaired glucose tolerance in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus
US5478852C1 (en) * 1993-09-15 2001-03-13 Sankyo Co Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of impaired glucose tolerance in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus

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CN1281358A (en) 2001-01-24
NO20001897D0 (en) 2000-04-12
IL135515A0 (en) 2001-05-20
ID24439A (en) 2000-07-20
OA11519A (en) 2004-02-09
GB9721692D0 (en) 1997-12-10
HRP20000256A2 (en) 2000-12-31
KR20010024482A (en) 2001-03-26
AU9547198A (en) 1999-05-03
AP2000001788A0 (en) 2000-06-30
NO20001897L (en) 2000-06-09
CZ20001298A3 (en) 2001-08-15
BG104405A (en) 2000-12-29
WO1999018944A1 (en) 1999-04-22
PL339804A1 (en) 2001-01-02
JP2001519383A (en) 2001-10-23
BR9815220A (en) 2000-11-14
UA66809C2 (en) 2004-06-15
HUP0003673A2 (en) 2001-10-28
HUP0003673A3 (en) 2001-12-28
CA2305289A1 (en) 1999-04-22
SK5322000A3 (en) 2000-09-12
EP1023057A1 (en) 2000-08-02
YU28700A (en) 2003-10-31
EA200000418A1 (en) 2000-10-30
TR200000957T2 (en) 2000-08-21

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