EP0975343A1 - Treatment of diabetes with thiazolidinedione and alpha-glucosidase inhibitor - Google Patents
Treatment of diabetes with thiazolidinedione and alpha-glucosidase inhibitorInfo
- Publication number
- EP0975343A1 EP0975343A1 EP98939513A EP98939513A EP0975343A1 EP 0975343 A1 EP0975343 A1 EP 0975343A1 EP 98939513 A EP98939513 A EP 98939513A EP 98939513 A EP98939513 A EP 98939513A EP 0975343 A1 EP0975343 A1 EP 0975343A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- compound
- administration
- glucosidase inhibitor
- pharmaceutically acceptable
- alpha glucosidase
- 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- Withdrawn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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Definitions
- This invention relates to a method of treatment, in particular to a method for the treatment of diabetes mellitus, especially non-insulin dependent diabetes (NIDDM) or Type II diabetes and conditions associated with diabetes mellitus.
- NIDDM non-insulin dependent diabetes
- Alpha glucosidase inhibitor antihyperglycaemic agents such as Acarbose, Emiglitate and Miglitol, are commonly used in the treatment of NIDDM (or Type II diabetes).
- European Patent Application, Publication Number 0,306,228 relates to certain thiazolidinedione derivatives disclosed as having antihyperglycaemic and hypolipidaemic activity.
- One particular thiazolidinedione disclosed in EP 0306228 is 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione (hereinafter 'Compound (I)').
- WO94/05659 discloses certain salts of Compound (I) including the maleate salt at example 1 thereof.
- Compound (I) is an example of a class of anti-hyperglycaemic agents known as 'insulin sensitisers'.
- Compound (I) is a thiazolidinedione insulin sensitiser.
- Another series of compounds generally recognised as having insulin sensitiser activity are those typified by the compounds disclosed in International Patent Applications, Publication Numbers WO93/21166 and WO94/01420. These compounds are herein referred to as 'acyclic insulin sensitisers'.
- Other examples of acyclic insulin sensitisers are those disclosed in United States Patent Number 5232945 and International Patent Applications, Publication Numbers WO92/03425 and WO91/19702. Examples of other insulin sensitisers are those disclosed in European Patent
- Compound (I) in combination with an alpha glucosidase inhibitor antihyperglycaemic agent provides a particularly beneficial effect on glycaemic control, with minimal adverse side effects, such combination is therefore particularly useful for the treatment of diabetes mellitus, especially Type II diabetes and conditions associated with diabetes mellitus.
- the invention provides a method for the treatment of diabetes mellitus, especially Type II diabetes and conditions associated with diabetes mellitus in a mammal such as a human, which method comprises administering an effective non-toxic and pharmaceutically acceptable amount of an insulin sensitiser, such as Compound (I), and an alpha glucosidase inhibitor antihyperglycaemic agent, to a mammal in need thereof.
- an insulin sensitiser such as Compound (I)
- an alpha glucosidase inhibitor antihyperglycaemic agent an effective non-toxic and pharmaceutically acceptable amount of an insulin sensitiser, such as Compound (I), and an alpha glucosidase inhibitor antihyperglycaemic agent
- the invention provides an insulin sensitiser, such as Compound (I), together with an alpha glucosidase inhibitor antihyperglycaemic agent for use in a method for the treatment of diabetes mellitus, especially Type II diabetes and conditions associated with diabetes mellitus.
- an insulin sensitiser such as Compound (I)
- an alpha glucosidase inhibitor antihyperglycaemic agent for use in a method for the treatment of diabetes mellitus, especially Type II diabetes and conditions associated with diabetes mellitus.
- the method comprises either co-administration of an insulin sensitiser, such as Compound (I), and an alpha glucosidase inhibitor antihyperglycaemic agent or the sequential administration thereof.
- an insulin sensitiser such as Compound (I)
- an alpha glucosidase inhibitor antihyperglycaemic agent or the sequential administration thereof.
- Co-administration includes administration of a formulation which includes both an insulin sensitiser, such as Compound (I), and a biguanide antihyperglycaemic agent or the essentially simultaneous administration of separate formulations of each agent.
- an insulin sensitiser such as Compound (I)
- an alpha glucosidase inhibitor antihyperglycaemic agent for use in the manufacture of a composition for the treatment of diabetes mellitus, especially Type II diabetes and conditions associated with diabetes mellitus.
- a suitable thiazolidinedione insulin sensitiser is Compound (I).
- Other suitable thiazolidinedione insulin sensitisers include (+) -5-[[4-[(3,4- dihydro-6-hydroxy-2,5J,8-tetramethyl-2H-l-benzopyran-2- yl)methoxy]phenyl]methyl]-2,4-thiazolidinedione (or troglitazone), 5-[4-[(l- methylcyclohexyl)methoxy]benzyl] thiazolidine-2,4-dione (or ciglitazone), 5-[4-[2-(5- ethylpyridin-2-yl)ethoxy]benzyl] thiazolidine-2,4-dione (or pioglitazone) or 5-[(2- benzyl-2,3-dihydrobenzopyran)-5-ylmethyl)thiazolidine-2,4-dione (or eng
- the method comprises the administration of 2 to 12 mg of Compound (I), especially when administered per day.
- the method comprises the administration of 2 to 4 , 4 to 8 or 8 to Particularly, the method comprises the administration of 2 to 4mg of Compound (I), especially when administered per day.
- the method comprises the administration of 4 to 8mg of Compound (I), especially when administered per day.
- the method comprises the administration of 8 to 12 mg of
- Compound (I) especially when administered per day.
- the method comprises the administration of 2 mg of Compound (I), especially when administered per day.
- the method comprises the administration of 4 mg of Compound (I), especially when administered per day.
- the method comprises the administration of 8 mg of Compound (I), especially when administered per day.
- the insulin sensitiser such as Compound (I) and the alpha glucosidase inhibitor antihyperglycaemic agent are each administered in a pharmaceutically acceptable form, including pharmaceutically acceptable derivatives such as pharmaceutically acceptable salts, esters and solvates thereof, as appropriate of the relevant pharmaceutically active agent.
- pharmaceutically acceptable derivatives such as pharmaceutically acceptable salts, esters and solvates thereof, as appropriate of the relevant pharmaceutically active agent.
- the names used for the relevant alpha glucosidase inhibitor may relate to a particular pharmaceutical form of the relevant active agent: It will be understood that all pharmaceutically acceptable forms of the active agents per se are encompassed by this invention.
- Suitable pharmaceutically acceptable forms of insulin sensitisers include those described in the above mentioned publications.
- Suitable pharmaceutically acceptable salted forms of Compound (I) include those described in EP 0306228 and WO94/05659.
- a preferred pharmaceutically acceptable salt is a maleate.
- Suitable pharmaceutically acceptable solvated forms of Compound (I) include those described in EP 0306228 and WO94/05659, in particular hydrates.
- Suitable pharmaceutically acceptable forms of the alpha glucosidase inhibitor antihyperglycaemic agent depend upon the particular agent used but includes known pharmaceutically acceptable forms of the particular compound chosen. Such derivatives are found or are referred to in standard reference texts such as the British and US Pharmacopoeias, Remington's Pharmaceutical Sciences (Mack Publishing Co.) and Martindale The Extra Pharmacopoeia (London, The Pharmaceutical Press) (for example see the 31st Edition page 341 and pages cited therein).
- the insulin sensitisers may be prepared using known methods, for example those disclosed in the above mentioned publications which are incorporated herein by reference.
- Compound (I) or, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof may be prepared using known methods, for example those disclosed in EP 0306228 and WO94/05659. The disclosures of EP 0306228 and WO94/05659 are incorporated herein by reference.
- Compound (I) may exist in one of several tautomeric forms, all of which are encompassed by the term Compound (I) as individual tautomeric forms or as mixtures thereof.
- Compound (I) contains a chiral carbon atom, and hence can exist in up to two stereoisomeric forms, the term Compound (I) encompasses all of these isomeric forms whether as individual isomers or as mixtures of isomers, including racemates.
- the alpha glucosidase inhibitor antihyperglycaemic agent of choice is prepared according to known methods, such methods are found or are referred to in standard reference texts, such as the British and US Pharmacopoeias, Remington's Pharmaceutical Sciences (Mack Publishing Co.) and Martindale The Extra Pharmacopoeia (London, The Pharmaceutical Press) (for example see the 31st Edition page 341 and pages cited therein).
- condition associated with diabetes includes those conditions associated with the pre-diabetic state, conditions associated with diabetes mellitus itself and complications associated with diabetes mellitus.
- condition associated with the pre-diabetic state' includes conditions such as insulin resistance, including hereditary insulin resistance, impaired glucose tolerance, obesity and hyperinsulinaemia.
- diabetes mellitus itself include hyperglycaemia, insulin resistance, including acquired insulin resistance and obesity. Further conditions associated with diabetes mellitus itself include hypertension and cardiovascular disease, especially atherosclerosis and conditions associated with insulin resistance. Conditions associated with insulin resistance include polycystic ovarian syndrome and steroid induced insulin resistance and gestational diabetes.
- Renal diseases associated with Type II diabetes include nephropathy, glomerulonephritis, glomerular sclerosis, nephrotic syndrome, hypertensive nephrosclerosis and end stage renal disease.
- the term 'pharmaceutically acceptable embraces both human and veterinary use: for example the term 'pharmaceutically acceptable' embraces a veterinarily acceptable compound.
- scalar amounts including mg amounts, of Compound (I) in a pharmaceutically acceptable form
- the scalar amount referred to is made in respect of Compound (I) per se:
- 2 mg of Compound (I) in the form of the maleate salt is that amount of maleate salt which contains 2 mg of Compound (I).
- Diabetes mellitus is preferably Type II diabetes.
- the particularly beneficial effect on glycaemic control provided by the treatment of the invention is indicated to be a synergistic effect relative to the control expected for the sum of the effects of the individual active agents.
- Glycaemic control may be characterised using conventional methods, for example by measurement of a typically used index of glycaemic control such as fasting plasma glucose or glycosylated haemoglobin (Hb Ale). Such indices are determined using standard methodology, for example those described in: Tuescher A, Richterich, P., Sau. med. Wschr. 101 (1971), 345 and 390 and Frank P., 'Monitoring the Diabetic Patent with Glycosolated Hemoglobin Measurements', Clinical Products 1988
- the dosage level of each of the active agents when used in accordance with the treatment of the invention will be less than would have been required from a purely additive effect upon glycaemic control.
- the treatment of the invention will effect an improvement, relative to the individual agents, in the levels of advanced glycosylation end products (AGEs), leptin and serum lipids including total cholesterol, HDL- cholesterol, LDL-cholesterol including improvements in the ratios thereof, in particular an improvement in serum lipids including total cholesterol, HDL- cholesterol, LDL-cholesterol including improvements in the ratios thereof.
- AGEs advanced glycosylation end products
- leptin and serum lipids including total cholesterol, HDL- cholesterol, LDL-cholesterol including improvements in the ratios thereof, in particular an improvement in serum lipids including total cholesterol, HDL- cholesterol, LDL-cholesterol including improvements in the ratios thereof.
- the active medicaments are preferably administered in pharmaceutical composition form.
- such compositions can include both medicaments or one only of the medicaments.
- compositions comprising an insulin sensitisers, such as Compound (I) especially 2 to 12 mg thereof, an alpha glucosidase inhibitor antihyperglycaemic agent and a pharmaceutically acceptable carrier therefor.
- an insulin sensitisers such as Compound (I) especially 2 to 12 mg thereof, an alpha glucosidase inhibitor antihyperglycaemic agent and a pharmaceutically acceptable carrier therefor.
- compositions are adapted for oral administration. However, they may be adapted for other modes of administration, for example parenteral administration, sublingual or transdermal administration.
- compositions may be in the form of tablets, capsules, powders, granules, lozenges, suppositories, reconstitutable powders, or liquid preparations, such as oral or sterile parenteral solutions or suspensions.
- a composition of the invention is in the form of a unit dose.
- Unit dose presentation forms for oral administration may be tablets and capsules and may contain conventional excipients such as binding agents, for example syrup, acacia, gelatin, sorbitol, tragacanth, or polyvinylpyrrolidone; fillers, for example lactose, sugar, maize-starch, calcium phosphate, sorbitol or glycine; tabletting lubricants, for example magnesium stearate; disintegrants, for example starch, polyvinylpyrrolidone, sodium starch glycollate or microcrystalline cellulose; or pharmaceutically acceptable wetting agents such as sodium lauryl sulphate.
- the compositions are preferably in a unit dosage form in an amount appropriate for the relevant daily dosage.
- Suitable dosages including unit dosages of the Compound of formula (I) comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 mg of Compound (I).
- the medicaments may be administered from 1 to 6 times a day, but most preferably 1 or 2 times per day.
- Particular dosages of Compound (I) are 2mg/day, 4mg/day, including 2mg twice per day, and 8 mg/day, including 4mg twice per day.
- Suitable dosages including unit dosages of the insulin sensitisers and the alpha glucosidase inhibitor antihyperglycaemic agent include the known dosages and unit doses for these compounds as described or referred to in reference texts such as the British and US Pharmacopoeias, Remington's Pharmaceutical Sciences (Mack Publishing Co.), Martindale The Extra Pharmacopoeia (London, The Pharmaceutical Press) (for example see the 31st Edition page 341 and pages cited therein) or the above mentioned publications.
- a typical daily dosage of acarbose is in the range of from 50 to 600 mg, an example lOOmg or 200mg per day.
- the solid oral compositions may be prepared by conventional methods of blending, filling or tabletting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are of course conventional in the art.
- the tablets may be coated according to methods well known in normal pharmaceutical practice, in particular with an enteric coating.
- Oral liquid preparations may be in the form of, for example, emulsions, syrups, or elixirs, or may be presented as a dry product for reconstitution with water or other suitable vehicle before use.
- Such liquid preparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminium stearate
- gel hydrogenated edible fats
- emulsifying agents for example lecithin, sorbitan monooleate, or acacia
- non-aqueous vehicles which may include edible oils
- almond oil fractionated coconut oil
- oily esters such as esters of glycerine, propylene glycol, or ethyl alcohol
- preservatives for example methyl or propyl p-hydroxybenzoate or sorbic acid
- conventional flavouring or colouring agents for example methyl or propyl p-hydroxybenzoate or sorbic acid.
- fluid unit dosage forms are prepared utilizing the compound and a sterile vehicle, and, depending on the concentration used, can be either suspended or dissolved in the vehicle.
- the compound can be dissolved in water for injection and filter sterilized before filling into a suitable vial or ampoule and sealing.
- adjuvants such as a local anaesthetic, a preservative and buffering agents can be dissolved in the vehicle.
- the composition can be frozen after filling into the vial and the water removed under vacuum.
- Parenteral suspensions are prepared in substantially the same manner, except that the Compound (I)s suspended in the vehicle instead of being dissolved, and sterilization cannot be accomplished by filtration.
- the compound can be sterilized by exposure to ethylene oxide before suspending in the sterile vehicle.
- a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound.
- Compositions may contain from 0.1% to 99% by weight, preferably from 10-60% by weight, of the active material, depending upon the method of administration.
- compositions may, if desired, be in the form of a pack accompanied by written or printed instructions for use.
- compositions are formulated according to conventional methods, such as those disclosed in standard reference texts, for example the British and US
- the present invention also provides a pharmaceutical composition
- a pharmaceutical composition comprising Compound (I), especially 2 to 12 mg thereof, an alpha glucosidase inhibitor antihyperglycaemic agent and a pharmaceutically acceptable carrier therefor, for use as an active therapeutic substance.
- the present invention provides a pharmaceutical composition
- a pharmaceutical composition comprising Compound (I), especially 2 to 12 mg thereof, an alpha glucosidase inhibitor antihyperglycaemic agent and a pharmaceutically acceptable carrier therefor, for use in the treatment of diabetes mellitus, especially Type II diabetes and conditions associated with diabetes mellitus.
- a range of 2 to 4mg includes a range of 2.1 to 4, 2.2 to 4, 2.3 to 4, 2.4 to 4, 2.5 to 4, 2.6 to 4, 2.7 to 4, 2.8 to 4, 2.9 to 4 or 3 to 4mg.
- a range of 4 to 8mg includes a range of 4.1 to 8, 4.2 to 8, 4.3 to 8, 4.4 to 8, 4.5 to 8, 4.6 to 8, 4.7 to 8, 4.8 to 8, 4.9 to 8, 5 to 8, 6 to 8 or 7 to 8mg.
- a range of 8 to 12 mg includes a range of 8.1 to 12, 8.2 to 12, 8.3 to 12, 8.4 to 12, 8.5 to 12, 8.6 to 12, 8.7 to 12, 8.8 to 12, 8.9 to 12, 9 to 12, 10 to 12 or 11 to 12mg.
- lactose monohydrate is passed through a suitable screen and blended with the milled maleate salt of Compound (I).
- Sodium starch glycollate, hydoxypropyl methylcellulose, microcrystalline cellulose and the remaining lactose are passed through a suitable screen and added to the mixture. Blending is then continued.
- the resulting mixture is then wet granulated with purified water.
- the wet granules are then screened, dried on a fluid bed drier and the dried granules are passed through a further screen and finally homogenised.
- the granules from above are placed into a tumble blender. Approximately two thirds of the lactose is screened and added to the blender. The microcrystalline cellulose, sodium starch glycollate, magnesium stearate and remaining lactose are screened and added to the blender and the mixture blended together. The resulting mix is then compressed on a rotary tablet press to a target weight of 150mg for the 1 , 2 and 4mg tablets and to a target weight of 300mg for the 8mg tablets.
- the tablet cores are then transferred to a tablet coating machine, pre-warmed with warm air (approximately 65 °C) and film coated until the tablet weight has increased by 2.0% to 3.5%.
- Aqueous film coating material 4.5 4.5 4.5 9.0
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Molecular Biology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (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)
- Fodder In General (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9712865.6A GB9712865D0 (en) | 1997-06-18 | 1997-06-18 | Novel method of treatment |
GB9712865 | 1997-06-18 | ||
GBGB9806708.5A GB9806708D0 (en) | 1998-03-27 | 1998-03-27 | Novel method |
GB9806708 | 1998-03-27 | ||
PCT/EP1998/003691 WO1998057635A1 (en) | 1997-06-18 | 1998-06-15 | Treatment of diabetes with thiazolidinedione and alpha-glucosidase inhibitor |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0975343A1 true EP0975343A1 (en) | 2000-02-02 |
Family
ID=26311746
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP98939513A Withdrawn EP0975343A1 (en) | 1997-06-18 | 1998-06-15 | Treatment of diabetes with thiazolidinedione and alpha-glucosidase inhibitor |
Country Status (24)
Country | Link |
---|---|
EP (1) | EP0975343A1 (no) |
JP (1) | JP2001523271A (no) |
KR (1) | KR20010013845A (no) |
CN (1) | CN1274282A (no) |
AP (1) | AP9901720A0 (no) |
AR (2) | AR014881A1 (no) |
AU (1) | AU8799998A (no) |
BG (1) | BG103966A (no) |
BR (1) | BR9810186A (no) |
CA (1) | CA2294134A1 (no) |
CO (1) | CO4940453A1 (no) |
DZ (1) | DZ2519A1 (no) |
EA (1) | EA200000040A1 (no) |
IL (1) | IL133138A0 (no) |
MA (1) | MA26510A1 (no) |
NO (1) | NO996270L (no) |
NZ (1) | NZ501345A (no) |
OA (1) | OA11631A (no) |
PE (1) | PE89199A1 (no) |
PL (1) | PL337577A1 (no) |
SK (1) | SK179499A3 (no) |
TR (1) | TR199903072T2 (no) |
UY (1) | UY25051A1 (no) |
WO (1) | WO1998057635A1 (no) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BR0009934A (pt) | 1999-04-23 | 2002-06-04 | Smithkline Beecham Plc | Produto farmacêutico |
CN100577175C (zh) | 2001-04-04 | 2010-01-06 | 奥索-麦克尼尔药品公司 | 包括葡萄糖重吸收抑制剂和ppar调节剂的联合疗法 |
US6838442B2 (en) | 2001-04-04 | 2005-01-04 | Ortho-Mcneil Pharmaceutical, Inc. | Combination therapy comprising glucose reabsorption inhibitors and retinoid-X receptor modulators |
FR2832930A1 (fr) * | 2001-12-03 | 2003-06-06 | Lipha | Composition pharmaceutique comprenant un inhibiteur d'alpha-glucosidase et un derive de thiazolidinedione et son utilisation pour la preparation de medicaments destines a traiter le diabete |
JP2004067575A (ja) * | 2002-08-06 | 2004-03-04 | Yaizu Suisankagaku Industry Co Ltd | 糖尿病治療薬効果促進剤 |
CN101121004B (zh) * | 2006-08-08 | 2010-07-21 | 鲁南制药集团股份有限公司 | 含有胰岛素增敏剂和米格列醇的药物组合物 |
CN101584705B (zh) * | 2008-05-24 | 2010-10-27 | 鲁南制药集团股份有限公司 | 一种治疗糖尿病及其并发症的药物组合物 |
CN101584688B (zh) * | 2008-05-24 | 2010-11-10 | 鲁南制药集团股份有限公司 | 一种治疗糖尿病及其并发症的药物组合物 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK0601001T3 (da) * | 1991-08-26 | 1997-10-20 | Upjohn Co | Flydende næringsmiddelprodukt indeholdende 3-guanidinopropionsyre. |
US5917052A (en) * | 1994-09-28 | 1999-06-29 | Shaman Pharmaceuticals, Inc. | Hypoglycemic agent from cryptolepis |
TWI238064B (en) * | 1995-06-20 | 2005-08-21 | Takeda Chemical Industries Ltd | A pharmaceutical composition for prophylaxis and treatment of diabetes |
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1998
- 1998-06-15 CA CA002294134A patent/CA2294134A1/en not_active Abandoned
- 1998-06-15 CN CN98806319A patent/CN1274282A/zh active Pending
- 1998-06-15 JP JP50375699A patent/JP2001523271A/ja not_active Ceased
- 1998-06-15 BR BR9810186-2A patent/BR9810186A/pt not_active IP Right Cessation
- 1998-06-15 PL PL98337577A patent/PL337577A1/xx unknown
- 1998-06-15 WO PCT/EP1998/003691 patent/WO1998057635A1/en not_active Application Discontinuation
- 1998-06-15 AU AU87999/98A patent/AU8799998A/en not_active Abandoned
- 1998-06-15 AP APAP/P/1999/001720A patent/AP9901720A0/en unknown
- 1998-06-15 TR TR1999/03072T patent/TR199903072T2/xx unknown
- 1998-06-15 EP EP98939513A patent/EP0975343A1/en not_active Withdrawn
- 1998-06-15 EA EA200000040A patent/EA200000040A1/ru unknown
- 1998-06-15 IL IL13313898A patent/IL133138A0/xx unknown
- 1998-06-15 SK SK1794-99A patent/SK179499A3/sk unknown
- 1998-06-15 KR KR1019997011866A patent/KR20010013845A/ko not_active Application Discontinuation
- 1998-06-17 MA MA25121A patent/MA26510A1/fr unknown
- 1998-06-17 AR ARP980102885A patent/AR014881A1/es unknown
- 1998-06-17 AR ARP980102882A patent/AR013352A1/es unknown
- 1998-06-17 DZ DZ980129A patent/DZ2519A1/xx active
- 1998-06-18 UY UY25051A patent/UY25051A1/es not_active Application Discontinuation
- 1998-06-18 PE PE1998000536A patent/PE89199A1/es not_active Application Discontinuation
- 1998-06-18 CO CO98034648A patent/CO4940453A1/es unknown
- 1998-07-15 NZ NZ501345A patent/NZ501345A/en unknown
-
1999
- 1999-12-08 BG BG103966A patent/BG103966A/bg unknown
- 1999-12-17 NO NO996270A patent/NO996270L/no not_active Application Discontinuation
- 1999-12-17 OA OA9900295A patent/OA11631A/en unknown
Non-Patent Citations (1)
Title |
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See references of WO9857635A1 * |
Also Published As
Publication number | Publication date |
---|---|
IL133138A0 (en) | 2001-03-19 |
AR013352A1 (es) | 2000-12-27 |
EA200000040A1 (ru) | 2000-08-28 |
NO996270D0 (no) | 1999-12-17 |
OA11631A (en) | 2004-11-22 |
JP2001523271A (ja) | 2001-11-20 |
NZ501345A (en) | 2001-10-26 |
MA26510A1 (fr) | 2004-12-20 |
PL337577A1 (en) | 2000-08-28 |
WO1998057635A1 (en) | 1998-12-23 |
UY25051A1 (es) | 2000-09-29 |
AU8799998A (en) | 1999-01-04 |
PE89199A1 (es) | 1999-10-23 |
KR20010013845A (ko) | 2001-02-26 |
SK179499A3 (en) | 2000-11-07 |
CN1274282A (zh) | 2000-11-22 |
AP9901720A0 (en) | 1999-12-31 |
BR9810186A (pt) | 2000-08-08 |
TR199903072T2 (xx) | 2000-07-21 |
NO996270L (no) | 1999-12-17 |
AR014881A1 (es) | 2001-04-11 |
CO4940453A1 (es) | 2000-07-24 |
BG103966A (bg) | 2000-07-31 |
CA2294134A1 (en) | 1998-12-23 |
DZ2519A1 (fr) | 2003-02-01 |
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