AP1287A - Treatment of diabetes with rosiglitazone and insulin. - Google Patents

Treatment of diabetes with rosiglitazone and insulin. Download PDF

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Publication number
AP1287A
AP1287A APAP/P/1999/001718A AP9901718A AP1287A AP 1287 A AP1287 A AP 1287A AP 9901718 A AP9901718 A AP 9901718A AP 1287 A AP1287 A AP 1287A
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Prior art keywords
compound
pharmaceutically acceptable
insulin
acceptable form
diabetes mellitus
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Application number
APAP/P/1999/001718A
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AP9901718A0 (en
Inventor
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
    • A61K31/435—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

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.
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 10 thiazolidinedione derivatives disclosed as having antihyperglycaemic and hypolipidaemic activity. One particular thiazolidinedione disclosed in EP 0306228 is 5-[4-[2-(N-methyl-N-(2-pyridyI)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.
International Patent Application, publication number WO97/05875 discloses a method for reducing the amount of exogenous insulin administered to a patient having NIDDM by administering a therapeutically effective amount of a thiazolidinedione derivative and/or a related compound.
It is now surprisingly indicated that a specific amount of Compound (I) in combination with insulin provides a particularly beneficial effect on glycaemic control, such combination is therefore particularly useful for the treatment of diabetes mellitus, especially Type II diabetes and conditions associated with diabetes mellitus.
Accordingly, 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.
Preferably, 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
In one particular aspect, the method comprises the administration of 2 to 12 mg of Compound (I), especially when administered per day.
V i kO / 6 6 /d/dV
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Particularly, the method comprises the administration of 2 to 4,4 to » or 8 to 12 mg of Compound (I) per day.
Particularly, the method comprises the administration of 2 to 4mg o~ Compound (I), especially when administered per day.
Particularly, the method comprises the administration of 4 to 8mg, sucn as greater than 4 for example 4.1, to 8 mg, of Compound (I), especially when administered per day.
Particularly, the method comprises the administration of 8 to 12 mg oi 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 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
2C those described in EP 0306228 and WO94/05659. A preferred pharmaceutically acceptable salt is a maleate.
Suitable pharmaceutically acceptable solvated forms of Compound (Ti inciude 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 31 st 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 m 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.
AP/P/8 9/0 1? 18
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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).
When used herein the term 'conditions 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 polycystic 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.
As used herein the term 'pharmaceutically acceptable' embraces both human and veterinary use: for example the term 'pharmaceutically acceptable' embraces a veterinarily 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 scalar amount referred to is made in respect of Compound (I) per se: For example 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., Schweiz, med. Wschr. 101 (1971), 345 and 390 and Frank P., 'Monitoring the Diabetic Patent with Glycosolated Hemoglobin Measurements', Clinical Products 1988
AP/?/ »9/01718
-3APlύ 1 2 8 Ί
In a preferred aspect, 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.
In the method of the invention, the active medicaments are preferably 5 administered in pharmaceutical composition form. As indicated above, such compositions can include both medicaments or one only of the medicaments.
In the treatment of the invention, insulin is usually administered by injection or by other known methods, for example those described in the reference texts mentioned herein. Thus the following comments relating to compositions,
Ϊ 0 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, they may be adapted for other inodes of administration, for example parenteral administration, sublingual or transdermal administration.
The compositions may be in the form of tablets, capsules, powders, granules, lozenges, suppositories, rcconstitutable powders, or liquid preparations, such as oral or steriie 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, maize-starch, calcium phosphate, sorbitol or glycine; tabietting lubricants, for example magnesium stearate; 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 of blending, filling or tabletting. Repeated blending operations may be used So 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 costed 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 oefore 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 .4.
AP C Ο 1 2 8 7 rt**·.
; - ι 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 parenterai 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 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. 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.
Compositions may, if desired, be in the form of a pack accompanied by written or printed instructions for use.
The 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).
In the treatments 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, 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
AP/P/99/01?!8
-5AP001287
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,
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.
No adverse toxicological effects have been established for the compositions or methods of the invention m the abovementioned dosage ranges.
The following example illustrates the invention but does not limit it in any way.
AP/P/89/01M8
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COMPOUND (I) COMPOSITIONS
A Concentrate Preparation
Approximately two thirds of the 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.
% COMPOSITION OF GRANULAR CONCENTRATE __
Ingredient Quantity (%)
AP/P/ 9 9 / 0 1 T 18
Milled Compound (I) as maleate salt 13.25 (pure maleate salt)
Sodium Starch Glycollate 5.00
Hydoxypropyl Methylcellulose 2910 5.00
Microcrystalline Cellulose 20.0
Lactose Monohydrate, regular grade to 100
Purified water *
* Removed during processing.
-7AP V Ο 1 2 8 7
B Formulation of the concentrate into tablets.
The granules from above an: 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 table! weight has increased by 2,9% to 3.5%.
AP/?/ 9 9/01/18
Quantity (mg per Tablet)
Tablet Strength l.Omg 2.0mg 4.0mg S.Omg
Active Ingredient:
Compound (I) maleate Concentrate granules 10.00 20.00 40.00 80.00
Other Ingredients:
Sodium Starch Glycollate 6.96 6.46 5.46 50.92
Microcrystalline Cellulose 27.85 25.85 21.85 43.70
Lactose monohydrate 104.44 96.94 81.94 163.88
Magnesium Stearate 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 Filin Coated Tablet 154.5 154.5 154.5 309.0

Claims (10)

1. A combination which comprises from 2 to 12 mg of 5-[A[2-(N-methyl’ N“(2-pyndyf)amino)ethoxy]benzyljthiazolidine-2.4-dione (Compound (fi) or a
5 pharmaceutically acceptable form thereof, and insulin.
2. A combination according to claim ±, comprising from 2 to 4, 4 to 8 or 8 to i2 mg or Uzompcuno. ii; or a pnarmaceuticaliv acceptable form tdereof.
jn according ro claim, 1 or claim 2, C mg ef Compound (Ϊ) or a pharmaceutically acceptable form thereof.
1 A r x. UULUOllldU^r -* ‘ ‘ ‘ ‘ 1 * ' r,-\ *1
4. A combination according to claim 1 or claim 2, comprising from to 8 mg of Compound (I) or a pharmaceutically acceptable form thereof.
o. A combination according t<_> claim 1 or claim 2. comprising from 8 to 12 r /--» i zrs i · it mi* ΠΤ * nmr'r'inTizO »»> γλτ· -s -----—--1 '-viAApvUuU va. AUCuyLdUld AUixll IA1C1 -Ui.
K A ^ηΓηΚιηηπηη nor'Arr'i^?!· οί »««-» 1 1 τ —
V. «. *. (v-u^iCiPuc. c.v ΛΛΟ-ν VUC Ul U-lAXiiiS 4 «.»*> J , U.2
20 of Compound (I) or a pharmaceutically acceptable form thereof.
8fX I· 0/66/^/4^
/. A combination according ro any one of claims 1 to 4, comprising 4 mg _ £ s-s i ZTS ί ' 11 + 1 .- « υι ccmpcuflc u; or a pnarmaceuticaiiy acceptable form thereoi.
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W «3_ΙΛ 1 i±l* VAA^ VA ^iCtllAAO A, Z-, *T <A12V J, U,1Uipi
8 mg or Co moon nd /) or - urir-qll--/ acceptable ton ,rm
9. A combination according to any one of claims 1 to 8. mherem Compound fit) or a pharmaceutically acceptable form thereof and insulin are
30 formulated as a single pharmaceutical composition.
AP 1 ύ12 8 7
-ιοί 0. A combination according to any one of claims 1 to 8, wherein
Compound (Γϊ or a pharmaceutically acceptable form thereof and insulin are formulated as separate pharmaceutical compositions.
11. A combination according to any one of claims 1 to 10, wherein compoinid (I) is present in the form of its maleate sait.
12. A pharmaceutical composition comprising from 2 to 12 nig of 5-[4-[2(N-methyl-N-(2-pyridyl)amino)ethoxyJbenzyl]thiazolidme-2,4-dione (Compound fl)) or a pharmaceutically acceptable form thereof, insulin and a pharmaceutically acceptable carrier therefor.
13. Use of from 2 to 12 nig of 5-[4-[2-(N-methyl-N-(2pyridyl)amino)ethoxy]benzyljthiazolidine-2,4-dione (Compound (1)) or a pharmaceutically acceptable form thereof and insulin in the manufacture of a medicament for use in the treatment of diabetes mellitus or a condition associated with diabetes mellitus.
14. Use of from 2 to 12 mg of 5-[4-[2-(N-methyl-N-(2pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione (Compound (I)) or a pharmaceutically acceptable form thereof in the manufacture of a medicament tor use with insulin in the treatment oi diabetes mellitus or a condition associated with diabetes mellitus.
15. Use of insulin in the manufacture of a medicament for use with from 2 to 12 mg oi 5-[4-f2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benz>’l]thia2olidine-2,4dione (Compound (I)) or a pharmaceutically acceptable form thereof in die treatment of diabetes mellitus or a condition associated with diabetes mellitus.
APAP/P/1999/001718A 1997-06-18 1998-06-15 Treatment of diabetes with rosiglitazone and insulin. AP1287A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9712866.4A GB9712866D0 (en) 1997-06-18 1997-06-18 Novel method of treatment
PCT/EP1998/003692 WO1998057636A1 (en) 1997-06-18 1998-06-15 Treatment of diabetes with rosiglitazone and insulin

Publications (2)

Publication Number Publication Date
AP9901718A0 AP9901718A0 (en) 1999-12-31
AP1287A true AP1287A (en) 2004-06-26

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APAP/P/1999/001718A AP1287A (en) 1997-06-18 1998-06-15 Treatment of diabetes with rosiglitazone and insulin.

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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)

* Cited by examiner, † Cited by third party
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 &amp; 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

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995007694A1 (en) * 1993-09-15 1995-03-23 Sankyo Company, Limited Use of thiazolidinediones to prevent or delay onset of 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
WO1997010819A1 (en) * 1995-09-18 1997-03-27 Ligand Pharmaceuticals Incorporated Treating niddm with rxr agonists

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995007694A1 (en) * 1993-09-15 1995-03-23 Sankyo Company, Limited Use of thiazolidinediones to prevent or delay onset of 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
WO1997010819A1 (en) * 1995-09-18 1997-03-27 Ligand Pharmaceuticals Incorporated Treating niddm with rxr agonists

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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
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