BG107605A - Tartarate salts of thiazolidinedione derivative - Google Patents

Abstract

A novel pharmaceutical compound 5-]4-2(N-methyl-N-2-pyridyl)amino)ethoxy]benzyl]thizolidine-2,4-di one Meso-Tartarate 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. 12 claims, 4 figures

Description

This invention relates to new pharmaceutical preparations, to a method for their preparation and to the use of pharmaceutical preparations in medicine.

BACKGROUND OF THE INVENTION

European Patent Application No. 0,306,228 relates to certain thiazolidinedione derivatives having hypoglycemic and hypolipidemic activity. The compound of Example 30 of EP 0,306,228 is 5- [4- [2- (1T-methyl-] N- (2-pyridyl) amino) ethoxy] benzyl] thiazolidine-2,4-dione (hereinafter compound ( I)).

International Patent Application WO94 / 05659 discloses certain salts of the compounds of EP 0,306,228, one of which is the tartrate salt. A preferred salt of WO94 / 05659 is the maleic acid salt.

SUMMARY OF THE INVENTION

It is now disclosed that compound (I) forms a new tartrate salt (hereinafter referred to as "meso-tartrate").

The new meso-tartrate is a stable, high melting crystalline substance, which is therefore suitable for bulk production and processing. Meso-tartrate undergoes a variety of pharmaceutical processing, especially in manufacturing processes that require or produce heat, such as grinding, fluidized bed drying, spray drying, hot melt and autoclave sterilization. Also meso9 · · · · · '* W, ·. ··. .: 21. :: ·.

Tartrate can be obtained by an efficient, economical and reproducible method, particularly suitable for large-scale production.

The new meso-tartrate also has useful pharmaceutical properties and appears to be particularly suitable for the treatment and / or prophylaxis of diabetes, conditions associated with diabetes and some of its complications.

Therefore, the present invention provides 5- [4- [2- (N-MeTHn-N (2-pyridyl) amino) ethoxy] benzyl] thiazolidine-2,4-dione, a mesotartarate salt or a solvate thereof.

Suitably, meso-tartrate is a mono-tartrate salt.

The mono-tartrate salts also optionally contain another monovalent salt-forming ion such as an alkali metal cation or an ammonium cation.

In a preferred embodiment, the meso-tartrate has an infrared spectrum substantially in accordance with Figure 1.

In one preferred embodiment, the meso-tartrate has a Raman spectrum, substantially in accordance with Figure 2.

In one preferred embodiment, the meso-tartrate has an X-ray powder diffraction pattern (XRPD) substantially in accordance with Table 1 or Figure

3.

In a preferred embodiment, the meso-tartrate has a 13C solid state NMR spectrum substantially in accordance with Figure 4.

In one preferred embodiment, the meso-tartrate has a melting point ranging from 147 to 157 ° C, such as 148 to 155 ° C, for example 148 ° C, 153 ° C and 155 ° C.

In a preferred embodiment, the invention provides 5- [4- [2- (N-methyl-N- (2-pyridyl) amino) ethoxy] benzyl] thiazolidine-2,4-dione, a mesotartarate salt, characterized in that it provides:

. ·. ··. . ; with:. :: ·.

· (I) the infrared spectrum essentially in accordance with Figure 1; and (n) a Raman spectrum, substantially in accordance with Figure 2; and (iii) X-ray powder diffraction pattern (XRPD) substantially in accordance with Table 1 or Figure 3;

and (iv) 13C solid state NMR spectrum substantially in accordance with Figure 4.

The present invention encompasses meso-gartarateb or its solvate isolated in pure form or in admixture with other materials. Therefore, in one embodiment, the meso-tartrate or solvate thereof is provided in _w isolated form.

In another embodiment, the meso-tartrate or solvate thereof is provided in purified form.

In another embodiment, the meso-tartrate or solvate thereof is provided in crystalline form.

The invention also provides meso-tartrate or a solvate thereof in a pharmaceutically acceptable solid form, such as a solid dosage form, especially adapted for oral administration.

The invention further provides the meso-tartrate or solvate thereof in a pharmaceutically acceptable form, especially in bulk, such form being particularly susceptible to pharmaceutical processing, especially in manufacturing processes which require or result in heat, such as milling; for example hot drying, in particular fluidized bed drying or spray drying; for example hot melt; such as hot sterilization such as in an autoclave.

In addition, the invention provides the meso-tartrate or solvate thereof in a pharmaceutically acceptable form, especially in bulk, and in particular in a form obtained in a manufacturing process that requires heat or generates heat, for example in ··· ··· ···· ground state; for example in hot-dried form, especially in fluidized bed-dried form or by spray-dried form; for example in a hot melt form; for example in a hot sterilized form such as in an autoclave.

A suitable solvate is the hydrate.

The invention also provides a process for the preparation of mesotartrate or a solvate thereof, characterized in that 5- [4- [2- (Nmethyl-N- (2-pyridyl) amino) ethoxy] benzyl] thiazolidine-2, -dione (compound (I)) or a salt thereof, preferably dispersed or dissolved in a suitable solvent, is reacted with a source of meso-tartrate ion and then, if necessary, a solvate of the resulting meso-tartrate is obtained; and the meso-tartrate or solvate thereof is recovered.

A suitable solvent for the reaction is a ketone for example acetone or an ether for example tetrahydrofuran, alkanol. such as propan-2-ol, a hydrocarbon such as toluene, an ester such as ethyl acetate, nitrile such as acetonitrile, or a halogenated hydrocarbon such as dichloromethane or water, or an organic acid such as acetic acid; or a mixture thereof.

Suitably, the meso-tartrate ion source is meso-tartaric acid. Meso-tartaric acid is preferably added in solid form or as a solution, for example in water or lower alcohol, such as methanol, ethanol, or propan-2-ol, or in a mixture of solvents. An alternative source of meso-tartrate ion is provided by a suitably soluble basic salt of meso-tartaric acid, for example ammonium meso-tartrate, or meso-tartrate of an amine, for example ethylamine or diethylamine.

The concentration of compound (I) is preferably in the range of 2 to 25% w / v, more preferably in the range of 5 to 20%. The concentrations of tartaric acid solutions are preferably in the range of 5 to 125% w / v.

• · · · · · · · · · · · · · · · · · · · · · · ·

Typically, the reaction is carried out at room temperature or at elevated temperature, for example at the reflux temperature of the solvent, although all suitable temperatures that provide the desired product can be used.

Solvates such as meso-tartrate hydrates are prepared by standard methods.

Extraction of the desired compound typically involves crystallization from a suitable solvent or mixture of solvents, usually from the reaction solvent, usually typically cooled. For example, meso-tartrate may crystallize a ketone such as acetone or ether such as tetrahydrofuran or water or a mixture thereof. Improved salt yields may be obtained by evaporation of part or all of the solvent or by crystallization at elevated temperature followed by controlled cooling, possibly in stages. Careful control of the sedimentation temperature can be used to improve the reproduction of the product form.

Crystallization can be initiated by the introduction of crystals of meso-tartrate or a solvate thereof, but this is not the main one.

If the mono-tartrate salt includes another monovalent salt-forming ion such as an alkali metal cation or an ammonium cation, said ion is conveniently obtained by reacting the monotartrate salt with a solution of a selected monovalent salt-forming ion, such as a metal or ammonium ion. Alternative compound (I) can be treated with the mono-tartrate salt of said monovalent salt-forming ion.

Compound (I) is prepared by known methods, such as those disclosed in EP 0,306,228 and WO94 / 05659. The disclosures of EP 0,306,228 and W094 / 05659 are cited herein.

Meso-tartaric acid is a commercially available compound.

··· £. · · · · · · · · · · · 9 9 · · · · 99 · · 9999 99 ··

As used herein, the term T _onset is generally defined by differential scanning calorimetry and has a meaning which is commonly understood in the art, such as in Pharmaceutical Thermal Analysis, Techniques and Applications, Ford and Timmins, 1989 - The temperature corresponding to the intersection of the baseline before the transition with the extrapolated front of the transition.

As used herein in connection with certain compounds, the term good flow properties is characterized by said compounds having a Hausner ratio of less than or equal to 1.5, especially less than or equal to 1.25.

"Hausner ratio" is a term used in the field.

As used herein, the term 'prevention of diabetes-related conditions' includes the treatment of conditions such as insulin resistance, impaired glucose tolerance, hyperinsulinemia and diabetes during pregnancy.

Diabetes means mainly type II diabetes.

Diabetes-related conditions include hyperglycemia and insulin resistance and obesity. Other conditions related to diabetes include hypertension, cardiovascular disease, especially atherosclerosis, certain eating disorders, specifically regulating appetite, and food intake by subjects suffering from malnutrition disorders, such as anorexia nervosa, and disorders, related to nutrition, such as obesity and anorexia bulimia. Other conditions associated with diabetes include polycystic ovaries and steroid-induced insulin resistance.

The complications of diabetes-related conditions covered herein include kidney disease, especially renal disease associated with the development of type II diabetes, including diabetic nephropathy, glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerotic sclerosis.

As mentioned above, the compounds of the invention have useful therapeutic properties: Accordingly, the present invention provides the meso-tartrate or a salt thereof for use as an active therapeutic substance.

In particular, the present invention provides the meso-tartrate or solvate thereof for use in the treatment and / or prophylaxis of diabetes, conditions associated with diabetes and certain complications thereof.

The meso-tartrate or solvate thereof may be administered alone or preferably as a pharmaceutical composition also containing a pharmaceutically acceptable carrier.

Suitable methods for formulating the meso-tartrate or solvate thereof are generally those described for compound (I) in the aforementioned publications.

Accordingly, the present invention also provides a pharmaceutical composition comprising meso-tartrate or a solvate thereof and a pharmaceutically acceptable carrier.

The meso-tartrate or solvate thereof is usually administered in a unit dosage form.

The active compound can be administered by any suitable route, but usually orally or parenterally. For such administration, the compounds are generally used in the form of a pharmaceutical composition together with a pharmaceutical carrier, diluent and / or excipient, although the exact form of the composition will naturally depend on the route of administration.

The formulations are prepared by blending and are suitable for oral, parenteral or topical administration, and as such may be in the form of tablets, capsules, liquid oral preparations, powders, granules, candies, lozenges, powders for powders. Preparation of solutions, injectable and infusion solutions or suspensions, suppositories and suppositories. transdermal agents.

Formulations for oral administration, especially formulated oral compositions, are preferred as they are more convenient for general use.

Tablets and capsules for oral administration are usually in unit doses and contain conventional excipients such as binders, fillers, diluents, tabletting agents, lubricants, disintegrants, colorants, flavors and wetting agents. The tablets may be coated according to methods known in the art.

Suitable excipients to be used include cellulose, mannitol, lactose and the like. Suitable disintegrants are starch, polyvinylpyrrolidone and starch derivatives such as sodium starch glycolate. Suitable lubricants include, for example, magnesium stearate. Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulfate.

Solid compositions for oral administration may be prepared by conventional methods of mixing, filling, tabletting or the like. Mixing operations can be repeated to allow the active substance to be distributed into formulations that use large amounts of fillers. Such operations, of course, are common in the art

Liquid preparations for oral administration may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or may be in the form of a dry product for preparation with water or other suitable solvent before use. Such liquid preparations may contain conventional additives, such as suspending agents, such as sorbitol, syrup, methylcellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel, or hydrogenated edible fats, emulsifiers, e.g. · · · · · · · · · · · · · · · · Monooleate, or acacia; non-aqueous solvents (which may include edible oils), for example, almond oil, fractionated coconut oil, oily esters such as glycerol esters, propylene glycol or ethyl alcohol; preservatives, for example methyl or propyl p-hydroxybenzoate or sorbic acid, and, if necessary, flavors and coloring agents.

For parenteral administration, the liquid unit dosage forms comprise a compound of the present invention and a sterile solvent. Depending on the solvent and the concentration, the compound may either be suspended or dissolved. Generally, parenteral solutions are prepared by dissolving the active compound in a solvent and filtering sterile before being filled into suitable vials or ampoules and sealed. Conveniently, excipients such as topical anesthetic and buffers are also dissolved in the solvent. To increase solubility, after filling in vials, the formulation may be frozen and the water removed in vacuo.

Parenteral suspensions are essentially prepared in the same way, except that the active substance is suspended in the solvent instead of dissolved and sterilized with ethylene oxide before being suspended in the sterile solvent. It is convenient to include a surfactant or a wetting agent in the composition to aid the even distribution of the active substance.

It is common practice for compositions to be accompanied by written or printed instructions for use in medical practice.

As used herein, the term "pharmaceutically acceptable" encompasses compounds, compositions and components for use in humanitarian and veterinary medicine, for example, the term "pharmaceutically acceptable salt" includes veterinary acceptable salt.

• · • · · · • · · · · ^υ · · · · · · • ft · ft ·· ft ··· ···· ·· · · · · · · · · ·

The present invention also provides a method for the treatment and / or prophylaxis of diabetes, conditions related to diabetes and certain complications thereof in mammals in humans and animals, which comprises administering an effective, non-toxic amount of mesotartrate or a solvate thereof to a human or animal mammal, in need.

It is appropriate to administer the active compound in the form of a pharmaceutical composition as defined above and this is a separate embodiment of the present invention.

In another embodiment, the present invention provides the use of meso-tartrate or a solvate thereof for the preparation of a medicament for the treatment and / or prophylaxis of diabetes, conditions associated with diabetes and certain complications thereof.

In the treatment and / or prophylaxis of diabetes, conditions associated with diabetes and certain complications thereof, the meso-tartrate or solvate thereof, are administered in amounts to provide compound (I) at appropriate doses, such as those disclosed in EP 0,306,228, WO94 / 05659. or WO98 / 55122.

No adverse toxicological effects were observed for the compounds of the invention in the aforementioned therapies.

Examples of carrying out the invention

The following examples illustrate the invention without limiting it in any way.

Example 1

5- [4- [2- (14-Methyl-1- (2-pyridyl) amino) ethoxy] -benzyl] -thiazolidine-2,4-dione meso-tartrate

A mixture of 5- [4- [2- (N-methyl-N- (2-pyridyl) amino) ethoxy] benzyl] thiazolidine-2,4-dione (8. 0 g) and tetrahydrofuran (160 ml) was stirred and heated to 50 ° C. A solution of meso-tartaric acid (3.84 g) in water (20 ml) was added and the mixture was stirred at 50 ° C for 15 ° C. · 9 99. * · ** ·· Cl ί 9 ⁹ 9 · I

9 9 9 9 9 9 9 99

9999 99 99 999999 99 minutes, filtered and the clear filtrate cooled to 21 ° C. The solvent was evaporated under reduced pressure at 40 ° C, acetone (40 ml) was added and the mixture was stirred at 21 ° C to give a white suspension. The product was combined by filtration, washed with acetone and dried in vacuo to give 5- [4- [2- (1-methyl N- (2-pyridyl) amino) ethoxy] benzyl] thiazolidine-2,4- dione meso-tartrate (10.6 g) as a white crystalline solid.

Example 2

5- [4- [2- (L-methyl-14- (2-pyridyl) amino) ethoxy] benzyl] thiazolidine 2,4,4 dione meso-tartrate

Mixture of 5- [4- [2- (N-methyl-14- (2-pyridyl) amino) ethoxy] benzyl] thiazolidine-2,4-dione (3.0 g, 8.4 mmol), acetone (40 ml) and tetrahydrofuran (5 ml) was heated at reflux for 2.5 hours with stirring. To this was added a solution of meso-tartaric acid monohydrate (1.41 g, 8.4 mmol) in water (2 ml). The reaction mixture was heated to reflux, stirred for 2.5 hours, then cooled to 21 ° C and stirred for 16 hours at 21 ° C. The white solid was collected by filtration, washed with acetone (40 ml) then dried under reduced pressure for 2.5 hours at 21 ° C to give 5- [4- [2- (N-methyl- 18 [- (2-pyridyl) amino) ethoxy] benzyl] thiazolidine-2,4-dione meso-tartrate (3.25 g) as a white crystalline solid.

Example 3

5- [4- [2- (L-methyl-N- (2-pyridyl) amino) ethoxy] benzyl] thiazolidine 2,4,4 dione meso-tartrate

Mixture of 5- [4- [2- (N-methyl-N- (2-pyridyl) amino) ethoxy] benzyl] thiazolidine-2,4-dione (10.0 g, 28 mmol), acetone (120 ml) and tetrahydrofuran (15 ml) was heated at reflux for 50 minutes with stirring. To this was added a solution of meso-tartaric acid monohydrate (4.7 g, 28 mmol) in water (6.0 · 1 * 4 · · · · · · · · 1 · Ζ · · · · · · · · · · · · · · · · · · · Ml). The reaction mixture was heated to reflux with stirring for 1 hour, then cooled to 21 ° C and stirred for 16 hours at 21 ° C. The white solid was collected by filtration, washed with acetone (50 ml) then dried under reduced pressure for 3 hours at 21 ° C to give 5- [4- [2- (N-methyl-1) - (2-Pyridyl) amino) ethoxy] benzyl] thiazolidine-2,4-dione meso-tartrate (11.7 g) as a white crystalline solid.

Happiness data registered for the product of Example 1

The infrared absorption spectrum of the product dispersion in mineral oil was obtained using a Nicolet 710 FT-IR spectrophotometer at 2 cm -1 resolution (Figure 1). Data are recorded at 1 cm-1 intervals. Bands are obtained at: 3405, 1738, 1694, 1629, 1556, 1537, 1505, 1459, 1436, 1418, 1330, 1268, 1249, 1223, 1182, 1167, 1143, 1104, 1074, 1057, 1033, 1000, 949 , 916, 887, 853, 818, 771, 717, 668, 619, 568, 528, 515 st-1.

The infrared spectrum of a solid is recorded using a Perkin-Elmer Spectrum One FT-IR spectrometer equipped with universal ATR accessories. Bands are obtained at: 3407, 2937, 2750, 1739, 1693, 1628, 1555, 1535, 1504, 1476, 1459, 1412, 1388, 1358, 1330, 1261, 1248, 1222, 1182, 1167, 1143, 1101, 1074 , 1056, 1033, 999, 948, 916, 887, 853, 818, 771, 744, 717, 667 cm-1.

The Raman spectrum of the product (Figure 2) was recorded with the sample in an NMR tube using a Nicolet 960 E. S. P. FT-Raman spectrometer at 4 cm-1 resolution with excitation by an Nd: V04 laser (1064 nm) with output power 400mW. The bands are examined at: 3101, 3059, 2952, 2922, 2877, 1739, 1604, 1544, 1458, 1438, 1394, 1331, 1270, 1222, 1203, 979, 887, 827, 739, 668, 638, 605, 472 , 344 cm-1.

The X-ray powder diffraction pattern of the product (Figure 3) is recorded using the following conditions: Anode: C, Generator voltage: 40 kV, Generator current: 40 mA, Initial angle: 2.0 ° 20, End angle: 35.0 ° 20, Step size : 0.02 ° 20, time step:

···.% · · · · · · · · · 19 · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

2.5 seconds. The characteristic XRPD angles and relative intensities are reported in Table 1.

Table 1.

Angle rel. intensity 2-theta ° 0% 4.9 11.4 9.3 12.4 9.9 3. 1 12.2 1.9 14.3 3.3 14.9 7 15.2 19 15.9 23. 8 16.2 13.9 17.0 8.6 17.3 17.5 18.1 25.9 18. 5 31.3 19.1 10.7 19.9 18.4 20.4 100 21.6 26 22.2 23.7 22.7 6.1 23.6 23.1 24.5 5.7 25.2 23 25.8 9.2 26.2 17.8 26.8 11.5 27.4 14.7

• · · · ·

28.1 6.8 28.4 8.7 29.7 5.7 30.2 9.7 30.6 9.3 31.1 23.6 31.4 13.4 32.2 14 32.6 19.7 32.9 15.2 33.6 11.4 33.8 12.4 34.4 8.7 34.7 9

The solid-state NMR spectrum (Figure 4) was recorded on a Bruker AMX360 apparatus operating at 90.55 MHz: The solid was placed in a 4 mm zirconium MAS rotor equipped with a Kel-F nozzle and rotating the rotor at about 10 kHz . The 13C MAS spectrum was realized by cross-polarization by Hartmann-Hahn protons (CP contact time 3ms, repetition period 15 s) and the protons were decuplicated during radiation using a two-pulse phase modulated (TPPM) composite sequence. The chemical shifts are related to the glycine carboxylate signal at 176.4 ppm relative to TMS and observed at: 183.0, 177.2, 175.4, 173.0, 160.0, 159.0, 151.8,

144.2, 138.9, 134.3, 130.8, 128.2, 123. 6, 113.7, 112.8, 77.4, 76.7, 74.5, 55.5, 53.5, 50.0, 42.4, 36.6, 33.8 ppm.

Properties of meso-tartrate

The solid phase stability of the meso-tartrate registered for the product of Example 1

The solid phase stability of the drug substance is determined by storing approximately 1.0 g of material in a glass vial at i) 4QOC / 75% RH (open air) for 1 month and b) at 50 ° C for 1 month. month. The material was tested by HPLC for final content and degradation products in both cases.

a) 40 C / 75% RH: No noticeable degradation was observed (HPLC analysis 97% of original).

b) 50oC: No noticeable degradation was observed (HPLC analysis 98% of original).

Melting point of meso-tartrate

The melting point of meso-tartrate is determined according to the method described in U. S. Pharmacopoeia, USP 23, 1995, Melting range or temperature, Procedure for Class 1a, using a Buchi 545 apparatus for determining the melting point.

Compound by an example 1, Point on melting: 149 ° C Compound by an example 2, Point on melting: 153 ° C Compound by an example 3, Point on melting: 155 ° C

Tonset of meso-tartrate

Tonset of the drug substance was determined by differential scanning calorimetry using a Perkin-Elmer DSC apparatus.

Claims (12)

1. Compound 5- {4- [2- (N- {yl-X- (2-pyridyl) amino) ethoxy] -benzyl] -thiazolidine-2,4-dione, meso-tartrate salt or solvate thereof. A compound according to claim 1, having: (i) the infrared spectrum substantially in accordance with Figure 1; (ii) Raman spectrum, mainly in accordance with Figure 2; (iii) X-ray powder diffraction pattern (XRPD) substantially in accordance with Table 1 or Figure 3; or (iv) the solid state NMR spectrum substantially in accordance with Figure 4. A compound according to claim 1 which has two or more of: (i) the infrared spectrum substantially in accordance with Figure 1; and (ii) a Raman spectrum, substantially in accordance with Figure 2; and (iii) X-ray powder diffraction pattern (XRPD) substantially in accordance with Table 1 or Figure 3; and (iv) the solid state NMR spectrum substantially in accordance with Figure 4. A compound according to any one of claims 1 to 3, in purified form. A compound according to any one of claims 1 to 3, in solid dosage form. A compound according to any one of claims 1 to 3, in a form susceptible to pharmaceutical processing in a manufacturing process that requires or produces heat, for example grinding; for example hot drying, in particular fluidized bed drying or spray drying; for example hot melt; such as hot sterilization such as in an autoclave. A compound according to any one of claims 1 to 3, in the form obtained in a manufacturing process requiring heat or in which heat is obtained, for example in a ground state; for example, in hot-dried form, especially in fluidized-bed fluid form or through • · ···· ·· ·· ···· ·· ·· atomizing a dried form; for example in hot melt form; for example in a hot sterilized form such as in an autoclave. A compound according to any one of claims 1 to 3, in a pharmaceutically acceptable form having good flowability. 9. A process for the preparation of meso-tartrate or a solvate thereof, characterized in that 5- [4- [2- (N-MeTHn-N- (2-pyridyl) amino) ethoxy] -benzyl] thiazolidine-2,4 -dione (compound (1)) or a salt thereof, reacts with a source of meso-tartrate ion and then, if necessary, a solvate of the resulting mesotartrate is obtained; and the meso-tartrate or solvate thereof is recovered. 10. A pharmaceutical composition comprising 5 [4- [2- (N-methyl-L- (2-pyridyl) amino) ethoxy] benzyl] thiazolidine-2,4 dione meso-tartrate or a solvate thereof, and a pharmaceutically acceptable carrier. 11. Compound 5- [4- [2- (T4-methyl-T4- (2-pyridyl) amino) ethoxy] benzyl] -thiazolidine-2,4-dione meso-tartrate or a solvate thereof for use as an active therapeutic substance . 12. Use of 5- [4- [2- (14-methyl-N- (2-pyridyl) amino) ethoxy] benzyl] -thiazolidine-2,4-dione meso-tartarag or a solvate thereof for the preparation of a medicament for treatment and / or the prevention of diabetes, conditions associated with diabetes and some of its complications.