CN1443186A - Thiazolidinedione salt for treatment of diabetes mellitus - Google Patents

Thiazolidinedione salt for treatment of diabetes mellitus Download PDF

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Publication number
CN1443186A
CN1443186A CN01813190A CN01813190A CN1443186A CN 1443186 A CN1443186 A CN 1443186A CN 01813190 A CN01813190 A CN 01813190A CN 01813190 A CN01813190 A CN 01813190A CN 1443186 A CN1443186 A CN 1443186A
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solvate
compound
thiazolidine
pyridyl
benzyl
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安德鲁·S·克雷格
蒂姆·C·T·霍
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SmithKline Beecham Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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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  • Chemical & Material Sciences (AREA)
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  • Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • General Chemical & Material Sciences (AREA)
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  • Hematology (AREA)
  • Obesity (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Endocrinology (AREA)
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  • Life Sciences & Earth Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)

Abstract

A novel pharmaceutical compound 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione hydrobromide or a solvate thereof, a process for preparing such a compound, a pharmaceutical composition comprising such a compound and the use of such a compound in medicine.

Description

The thiazolidinedione salt that is used for treating diabetes
The present invention relates to novel medicine, the method for making of this medicine and the purposes of this medicine in medical science.
Publication number is that 0306228 european patent application relates to the active thiazolidine diketone derivative that some have lowering blood glucose according to reports and impel serum lipid to reduce.The compound of the embodiment 30 of EP 0306228 is 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2,4-diketone (below be called " compound (I) ").
Publication number is some salt that the international patent application of WO 94/05659 has disclosed the compound of EP 0306228, comprises by mineral acid such as Hydrogen bromide, hydrochloric acid and sulfuric acid, and the salt that forms of organic acid such as methylsulfonic acid, tartrate and particularly toxilic acid.
Have found that compound (I) forms novel hydrobromate (below be also referred to as " hydrobromide " (" Hydrobromide ")), it is stable especially, therefore is suitable for large-scale preparation and handles.This hydrobromide also has high-melting-point, shows special good water-solubility and has good bulk flow.Therefore this hydrobromate makes us carrying out uncannily particularly grinding on a large scale of large-scale medicine processing.
This novel form can be made by enough renewable production arts effective, economic and that be particularly suitable for mass preparation.
This novel hydrobromide also has useful pharmaceutical properties, and particularly people point out, and it is useful to diabetes, disease and the treating and/or preventing of its complication relevant with diabetes.
Therefore, the invention provides Hydrogen bromide 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2,4-diketone or its solvate.
What this hydrobromide was suitable for is single hydrobromide.
One preferred aspect, this hydrobromide has and figure I consistent basically infrared spectra.
One preferred aspect, this hydrobromide has and figure II consistent basically Raman spectrum.
One preferred aspect, this hydrobromide has and Table I or figure III consistent basically X-ray powder diffraction pattern (XRPD).
One preferred aspect, this hydrobromide has consistent basically solid-state with figure IV 13The CNMR spectrum.
The fusing point of this hydrobromide is 175～185 ℃ a scope, and particularly 180～185 ℃ for example are 181 ℃, and this also is preferred.
In addition, the T of this hydrobromide BeginningBe 180-186 ℃ scope, for example 182.5 ℃.
Therefore, one preferred aspect, this hydrobromide is characterised in that it has in the following feature two or more:
(i) basically with figure I consistent infrared spectra;
(ii) basically with figure II consistent Raman spectrum;
(iii) basically with Table I or figure III consistent X-ray powder diffraction pattern (XRPD);
(iv) consistent with figure IV basically is solid-state 13The CNMR spectrum;
(v) melting range is 175～185 ℃, particularly 180～185 ℃, and for example 181 ℃.
The present invention includes the hydrobromide that is separated into pure form or its solvate or with the mixture of other materials.Therefore, on the one hand, the invention provides the hydrobromide that is in separation configuration or its solvate.
On the other hand, the invention provides the hydrobromide that is in pure form or its solvate.
Aspect another, the invention provides the hydrobromide that is in crystal habit or its solvate.
In addition, the invention provides and be in the hydrobromide that can accept form on the solid-state drug or its solvate, for example solid dosage is specially adapted to do oral.
In addition, the present invention also provides and is in the hydrobromide that can accept form on the medicine or its solvate, particularly is in loose form, and this form is easy to grind especially.
Also have, the invention provides and be in the hydrobromide that can accept form on the medicine or its solvate, particularly be in loose form, this form has good fluidity, particularly good bulk flow.
The solvate that is fit to is a hydrate.
The present invention also provides the method for the described hydrobromide of preparation or its solvate, it is characterized in that preferably being scattered in or being dissolved in 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group in the suitable solvent] benzyl] thiazolidine-2,4-diketone or its salt, react with the bromination hydrogen source, then, if desired, the solvate for preparing this hydrobromide; And reclaim this hydrobromide and solvate thereof.
The reaction solvent that is fit to is alkanol such as propyl alcohol-2, or hydrocarbon such as toluene, ketone such as acetone, ester such as ethyl acetate, ether such as tetrahydrofuran (THF), nitrile such as acetonitrile, or halohydrocarbon such as methylene dichloride, water, or organic acid such as acetate; Or their mixture.
The bromination hydrogen source can be easily with aqueous solution of hydrogen bromide for example the 48%w/w aqueous solution provide.This bromination hydrogen source also can be a hydrogen bromide at suitable solvent also can be for example solution in the propyl alcohol-2 of reaction solvent.In addition, hydrogen bromide can directly be added among the solution or suspension of compound (I) in selected reaction solvent.
The another kind source of the hydrogen bromide subsalt such as the brometo de amonio of hydrogen bromide, or the hydrobromate of amine such as ethamine or diethylamine provides.
Reaction is carried out under room temperature or high temperature usually, for example carries out under the reflux temperature of solvent, though also can adopt any suitable temp that can generate required product.
The solvate of this hydrobromide for example hydrate is produced according to common method for making.
The recovery of required compound generally comprises by for example 20～25 ℃ or 40～50 ℃ of scopes that usually it are cooled to 0 ℃～60 ℃, and crystallizes out from suitable solvent (suitable is reaction solvent).For example, this hydrobromide can crystallize out as propyl alcohol-2 or ketone such as acetone from alcohol.
In a kind of preferred form, recovery is cooled to for example 40～50 ℃ scope of first temperature at the beginning of comprising handle, produces crystallization originally thus, is cooled to second temperature then, and OK range is 0～25 ℃.
Crystallization also can be inoculated and begins with the crystallization of hydrobromide or its solvate, but this is unessential.
Use appropriate method to make solvate.
Compound (I) is according to the known method preparation, for example according to preparing at EP 0306228 and WO 94/05659 those disclosed method.Document for referencial use is quoted in being disclosed in of EP 0306228 and WO 94/05659 here.
Use term " T when here Beginning" time; it is measured with dsc usually; and have the meaning that the present technique field is all understood; for example at Ford and Timmins; among 1989 " drug fever analysis; method and application " (Pharmaceutical Thermal Analysis, Techniques andApplications) that shown with " corresponding to the temperature of the intersection of the pre-transition baseline that has extrapolation transition forward position " expressed meaning.
When using term with regard to some compound here, term " good flowing property " is characterized by the Hausner of this compound suitably than for being less than or equal to 1.5, particularly is less than or equal to 1.25.
" Hausner ratio " is the term that the present technique field is accepted.
When using term here, term " prevention of the disease relevant with diabetes " comprises those diseases of treatment, as insulin resistance, and the sugar tolerance that is weakened, hyperinsulinemia, and gestational diabetes.
Diabetes preferably refer to type ii diabetes.
The disease relevant with diabetes comprises hyperglycemia and insulin resistance and obesity.In addition, the disease relevant with diabetes also comprises hypertension, cardiovascular disorder is atherosclerosis particularly, some eating disorder, particularly suffer from disease such as the anorexia nervosa relevant, and suffer from the disease relevant such as obesity and the bulimiac patient's of apocleisis appetite stimulator and intake adjusting with overfeeding with dietary deficiency.The other diseases relevant with diabetes also comprises the insulin resistance that polycystic ovary syndrome and steroidal cause.
The complication of the disease relevant with diabetes that comprises here comprises kidney disease, and particularly with the relevant ephrosis of type ii diabetes development, this comprises that diabetic nephropathy becomes, glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, and final stage ephrosis.
As mentioned above, compound of the present invention has useful curative properties: therefore the invention provides hydrobromide or its solvate as the active treatment material.
More particularly, the invention provides be used for the treatment of and/or prevent diabetes, the disease relevant with diabetes with and hydrobromide or its solvate of some complication.
This hydrobromide or its solvate itself get final product administration, and perhaps it is preferably also to comprise the pharmaceutical composition administration of pharmaceutically acceptable carrier.The appropriate method of preparing this hydrobromide or its solvate normally in above-mentioned publication about disclosed those methods of compound (I).
Therefore, the present invention also provides a kind of pharmaceutical composition that comprises described hydrobromide or its solvate and pharmaceutically acceptable carrier.
This hydrobromide or its solvate are generally with the unit dosage form administration.
This active compound can be with any suitable pathways administration, but normally per os or parenteral approach.For this usage, this compound uses with the form of pharmaceutical composition with pharmaceutical carrier, thinner and/or vehicle usually, though the accurate form of pharmaceutical composition will depend on administering mode naturally.
This composition is with being mixed and made into, and is applicable to oral, parenteral or topical, makes tablet, capsule, oral liquid for this reason, powder, granula, lozenge, ingot, dissolved powder again, injectable or non-fus solution or suspension, suppository and the device that uses through skin.But oral compositions is preferred, and the oral compositions of Cheng Xinging particularly is because they are suitable for common usage.
The tablet or the capsule of mouth administration provide with unitary dose usually, and contain vehicle commonly used such as binding agent, filler, and thinner becomes tablet, lubricant, disintegrating agent, tinting material, perfume compound, and wetting agent.These tablets can coat by method well-known in the art.
Used suitable filler comprises Mierocrystalline cellulose, mannitol, lactose and other resemblances.The disintegrating agent that is suitable for comprises starch, polyvinylpyrrolidone and starch derivative such as Explotab.The lubricant that is suitable for comprises for example Magnesium Stearate.The pharmaceutically acceptable wetting agent that is suitable for comprises Sodium Lauryl Sulphate BP/USP.
Can adopt the method such as blending, filling, compressing tablet of common usefulness to make solid-state oral compositions.Can adopt the methodology of repetition blending that promoting agent is distributed in the composition that has used mass filler.Certainly, this present technique field that operates in is used always.
The form of liquid-state preparation can be for example aqeous suspension or oil suspension, solution, and emulsion, syrup, or elixir, perhaps it can provide with the dry labor thing, and this dry labor thing water or other suitable medium things before use dissolves again.This liquid formulation can contain typical additives for example suspension agent such as sorbyl alcohol, syrup, methylcellulose gum, gelatin, Natvosol, carboxymethyl cellulose, aluminium stearate gel or hydrogenation edible fat, emulsifying agent such as Yelkin TTS, polyoxyethylene-sorbitan mono-oleate or gum arabic; Non-water vehicle (it can comprise edible oil) is as Prunus amygdalus oil, fractionated coconut oil, oily ester such as glyceryl ester, propylene glycol ester or ethanol ester; Sanitas such as methyl p-hydroxybenzoate or propyl ester or Sorbic Acid; And also can contain suitable perfume compound or tinting material if desired.
For parenteral admin, prepared and contained The compounds of this invention and aseptic vectorial liquid unit dosage agent form.According to vehicle and concentration, this compound can be suspended or dissolving.Parenteral solution usually by be dissolved in this active compound in the vehicle, filter-sterilized and seal and produce before pouring into suitable phial or ampoule.Assistant agent such as local anesthetic, sanitas and buffer reagent also be dissolved in the vehicle also be good.For improving stability, after under pouring into phial and vacuum, dewatering, can this composition is freezing.
Parenteral suspension makes with basic identical method, and different is, in being suspended in sterilization vehicle before, this active compound is suspended in the vehicle, rather than makes it dissolving and be exposed to make it sterilization in the oxyethane.In composition, comprise tensio-active agent or wetting agent so that the active compound uniform distribution is useful.
The common way is that in the use of relevant pharmacotherapy, this composition is usually with using method that write or printing.
Terminology used here " pharmaceutically acceptable " comprises compound, composition and each composition, but both humans, and also can be for animals: for example term " pharmaceutically acceptable salt " comprises acceptable salt on the veterinary drug.
The present invention also provide treat and/or prevent people or inhuman mammiferous diabetes, the disease relevant with diabetes with and the method for some complication, this method comprises hydrobromide or its solvate to the people of needs or the effective nontoxic amount of non-human mammal administration.
This active constituent is easily with pharmaceutical composition administration defined above, and this constitutes a special aspect of the present invention.
On the other hand, the invention provides this hydrobromide and solvate thereof in the purposes of making aspect the medicine, this medicine is used for the treatment of and/or prevent diabetes, the disease relevant with diabetes with and some complication.
Treat and/or prevent diabetes, the disease relevant with diabetes with and during some complication, the usage quantity of hydrobromide and solvate thereof should make can provide the compound of suitable dose (I), for example EP 0306,228, and is disclosed among WO 94/05659 or the WO 98/55122.
For compound of the present invention, in above-mentioned treatment, find no harmful toxicological effect.
The following example will be explained the present invention, but in no case be restriction the present invention.Embodiment 1: Hydrogen bromide 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2, the 4-diketone
With 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine 2,4-diketone (1.0 gram) stirs and is heated to 10 fens clock times of backflow with the mixture of propyl alcohol-2 (50 milliliters), observes clear solution at the moment.Dropwise add Hydrogen bromide (the 48%w/w aqueous solution, 0.31 milliliter) then, under refluxing, stirred this reaction mixture 10 minutes, make it to be cooled to 21 ℃ then.Filter and collect product, and, obtain white crystalline solid Hydrogen bromide 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group with propyl alcohol-2 (10 milliliters) washing] benzyl] thiazolidine-2,4-diketone (0.41 gram).Embodiment 2: Hydrogen bromide 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2, the 4-diketone
With 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2,4-diketone (3.0 gram) stirs and is heated to 15 fens clock times of backflow with the mixture of acetone (10 milliliters), observes clear solution at the moment.Add Hydrogen bromide (the 48%w/w aqueous solution, 0.95 milliliter) then, under refluxing, stirred this reaction mixture 15 minutes, make it to be cooled to 21 ℃ then.Place after 120 hours, decant removes mother liquor, with acetone (10 milliliters) wash crystallization product, and under vacuum dry 3 hours, obtain Hydrogen bromide 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2,4-diketone (3.7 gram).1H-NMR (d6-dimethyl sulfoxide (DMSO)): with the Hydrogen bromide 5-[4-[2-that contains acetone (0.5%w/w) (N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2,4-diketone unanimity.Embodiment 3: Hydrogen bromide 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2, the 4-diketone
With 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2,4-diketone (15.0 gram) stirs with the mixture of acetone (230 milliliters), and is heated to backflow 15 minutes, observes clear solution at the moment.Add Hydrogen bromide (the 48%w/w aqueous solution, 4.75 milliliters) then, this reaction mixture is cooled to 45 ℃, and stirred 1 hour, be chilled to 21 ℃ then.Filter and collect white solid, and, get white crystalline solid Hydrogen bromide 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group with acetone (100 milliliters) washing] benzyl] thiazolidine-2,4-diketone (17.7 gram).The record of the characteristic of this hydrobromide (1) embodiment 3 products
The solubleness of this hydrobromide
This solubility of substances, by will adding to about 100 milligrams of medicines from 1 milliliter of water to 1000 milliliters of components, till this powder has dissolved and record, this visual solubleness is used the HPLC to saturated solution to analyze and is confirmed.
Solubleness: the solid-state stability of 6 these hydrobromides of mg/ml:
The solid-state stability of this medicine, about 1.0 these materials of gram that will be in vial under following situation and measure it: i) in 40 ℃/relative humidity (RH) 75%, open bottle, 1 month, b) at 50 ℃, filled in bottle, 1 month.Measure the final content and the degraded product of this material in both cases with HPLC.
A) 40 ℃/75%RH: do not observe tangible degraded (HPLC measures and contains initiator 98%).
B) 50 ℃: do not observe tangible degraded (HPLC measures and contains initiator 98%).The flowing property of this hydrobromide:
(see " science of medicine-dosage form design " (" Pharmaceutics-TheScience of Dosage Form Design ") with standard method, editor M.Aulton, 1988, publish by ChurchillLivingstone) measure the tap density and the ratio between the bull tap density (tappedbulkdensity) (Hausner compares) of this hydrobromide.
The Hausner ratio; 1.3 the T of this hydrobromide Beginning
With the T of Perkin-Elmer DSC7 instrument with this medicine of determine with dsc method Beginning
T Beginning: 182.5 ℃
The fusing point of this hydrobromide
Use the fusing point of visual this medicine of mensuration of warm rank microscope.
Fusing point: 181 ℃.(2) record of embodiment 2 products
With Nicolet 710 FT-IR spectrographs at 2cm -1Record the infrared absorption spectrum (figure I) of the dispersion thing of this product in mineral oil under the resolution.With 1cm -1At interval these data are carried out digitizing.Observe each absorption band at following place: 2923,2854,2749,1745,1698,1643,1610,1544,1515,1459,1419,1378,1327,1313,1287,1256,1240,1228,1203,1185,1151,1071,1054,1032,1014,985,906,803,771,738,712,524cm -1
Write down the IR spectrum of this solid product with general ATR instrument.Observe each absorption band at following place: 2929,2859,2749,1745,1694,1641,1608,1543,1514,1445,1419,1382,1358,1326,1311,1287,1255,1240,1202,1184,1148,1070,1053,1031,1014,985,906,862,844,802,768,737,710,657cm -1Adopt Nicolet 960 E.S.P.FT-Raman spectrographs, at 4cm -1Under the resolution, be that the Nd:V04 laser (1064nm) of 400mw excites, use the sample in the NMR pipe, note the Raman spectrum (figure II) of product with output rating.Observe each absorption band at following place: 3067,2997,2926,2884,2960,1747,1611,1588,1545,1445,1382,1360,1315,1287,1240,1213,1185,1070,1016,986,917,826,769,740,712,659,636,620,605,506,470,405,332,303,134,99cm -1
Adopt the XRPD figure (figure III) of following contact conditions record product: sleeve cathode: Cu, producer voltage: 40Kv, producer electric current: 40mA, initial angle: 2.0 ° of 2 θ, end angle: 35.0 ° of 2 θ goes on foot wide: 0.02 ° of 2 θ, per time in step: 2.5 seconds.Feature XRPD angle and relative intensity are recorded in the table 1.
Table 1
The angle Intensity
????2θ° ????％
????10.0 ????2.9
????11.7 ????2.7
????12.4 ????0.8
????13.2 ????8.9
????13.4 ????9.6
????13.8 ????1.1
????14.4 ????1.8
????14.8 ????5.6
????15.9 ????7.4
????16.3 ????23.5
????17.1 ????17.2
????17.6 ????15.5
????18.1 ????21.1
????19.4 ????15.1
????20.3 ????6.8
????20.7 ????2.4
????21.3 ????7.3
????22.1 ????36.3
????22.5 ????20.8
????22.8 ????3
????23.4 ????100
????23.7 ????18
????24.0 ????19.7
????24.5 ????18.1
????24.9 ????25.2
????25.7 ????10.6
????26.3 ????12
????26.8 ????11.8
????27.0 ????15.8
????27.3 ????6.6
????27.8 ????15.4
????28.2 ????5
????29.2 ????12.4
????29.4 ????6.8
????29.9 ????5.9
????30.4 ????11.5
????30.7 ????21.9
????31.1 ????2.9
????31.8 ????7.2
????32.2 ????8.3
????32.3 ????8.8
????32.5 ????11.9
????33.0 ????7.3
????33.9 ????7
????34.3 ????9
????34.7 ????5.5

Claims (10)

1. a compound Hydrogen bromide 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2,4-diketone and solvate thereof.
2. according to the compound of claim 1, it is characterized in that it has in the following feature two or more:
(i) basically with figure I consistent infrared spectra;
(ii) basically with figure II consistent Raman spectrum;
(iii) basically with Table I or figure III consistent X-ray powder diffraction pattern (XRPD);
(iv) consistent with figure IV basically is solid-state 13The CNMR spectrum;
(v) melting range is 175～185 ℃, particularly 180～185 ℃, for example is 181 ℃.
3. according to the compound of claim 1 or 2, it is in the form of purifying.
4. according to each compound of claim 1～3, it is in the solid dosage form.
5. according to each compound of claim 1～3, it is in polished pharmaceutically acceptable form.
6. according to each compound of claim 1～3, it is in the pharmaceutically acceptable form with good flow performance.
7. one kind prepares Hydrogen bromide 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2, the method for making of 4-diketone or its solvate, it is characterized in that 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2,4-diketone or its salt and the reaction of bromination hydrogen source, then, if desired, the solvate for preparing this hydrobromide; And reclaim this hydrobromide and solvate thereof.
8. one kind comprises Hydrogen bromide 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2,4-diketone or its solvate and be the pharmaceutical composition of its used pharmaceutically acceptable carrier.
9. compound Hydrogen bromide 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group as the active treatment material] benzyl] thiazolidine-2,4-diketone or its solvate.
10. Hydrogen bromide 5-[4-[2-(N-methyl-N-(2-pyridyl) amino) oxyethyl group] benzyl] thiazolidine-2,4-diketone or its solvate preparation be used for the treatment of and/or the medicine of prevent diabetes, the disease relevant and some complication thereof with diabetes aspect purposes.
CN01813190A 2000-06-08 2001-06-08 Thiazolidinedione salt for treatment of diabetes mellitus Pending CN1443186A (en)

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DE102005034406A1 (en) * 2005-07-22 2007-02-01 Ratiopharm Gmbh New salts of rosiglitazone
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