UA82833C2 - CRYSTAL SODIUM TELMISARTAN AND ITS APPLICATION AS ANGIOTENZINE ANTAGONIST - Google Patents

Abstract

The invention relates to a crystalline sodium salt of 4'-[2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazol-1-ylmethyl]biphenyl-2-carboxylic acid (INN: Telmisartan), to a method for the production thereof and to the use of the same for producing a pharmaceutical having an angiotensin II antagonistic action.

Description

Description of the invention

This invention relates to the crystalline sodium salt of 2 4-(2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazol-1-ylmethyl|biphenyl-2-carboxylic acid (international non-proprietary name telmisartan), the method of its preparation, as well as its use for the preparation of the corresponding medicinal product.

Prerequisites for creating an invention

The compound telmisartan is known from the application EP 502314 B1 and has the following chemical structure:

Me

M Me

And to: M

M M and O- DON p 29 fi o

Telmisartan, as well as its physiologically compatible salts, have valuable pharmacological properties.

Telmisartan is an angiotensin antagonist, primarily an angiotensin II antagonist, which due to its pharmacological properties can be used, for example, for the treatment of hypertension and heart failure, for the treatment of local blood circulation disorders, cardiac ischemia (angina), for the prevention of further development of heart failure after a myocardial infarction , for the treatment of diabetic neuropathy, with glaucoma, diseases of the gastrointestinal tract, as well as diseases of the urinary bladder. Information about the possible use of telmisartan in other fields of therapy can be gleaned from the application EP 502314 VI, which in this part is incorporated into this description by reference. everything

Telmisartan is a commercially available product and is supplied under the trade name MisagaizF). The pharmaceutical form, in which telmisartan is offered on the market, is obtained from the free acid of telmisartan using the spray drying method, which requires significant costs. As a result of the low solubility of the free acid, the practical implementation of less expensive methods of obtaining an alternative dosage form is also associated with significant difficulties. "

Taking into account the above, the basis of this invention was the task of offering telmisartan in a form that would allow obtaining the medicinal form of this active substance in a simpler and cheaper way. At the same time, it was necessary to take into account the fact that, in principle, the preparation of a composition that "contains" the relevant medicinal active substance requires compliance with various parameters, which in turn are somehow related to the properties of this active substance. Examples of such parameters include, but are not limited to, the stability of the activity of the starting substance in various environmental conditions, stability in the process of obtaining a pharmaceutical composition, as well as stability in the final compositions of the medicinal product. When creating the invention, it was further assumed that the active substance used in the preparation of the above-mentioned medicinal compositions should have the highest possible degree of purity and remain stable during long-term storage, regardless of the surrounding conditions. This requirement is due to the need to prevent in the future, when using medicinal compositions, the presence in them, along with the actual active substance, for example, of possible products of its decomposition. In this case, the content of the active substance in the dosage forms may later turn out to be lower than necessary.

Another important condition for obtaining solid dosage forms, necessary for achieving high pharmaceutical quality of the medicinal composition, is ensuring extremely stable, crystalline morphology of the active substance. Failure to comply with this requirement can lead to a change in the morphology of the active substance in certain cases under the conditions of receiving the appropriate dosage form. Such a change, in one way or another, may affect the reproducibility of the method of preparation and will not allow obtaining target compositions that meet the high requirements for the quality of medicinal compositions. Based on this principle, any the possibility of changing the state of the solid substance in the medicinal product, which will allow to improve its physical and chemical stability in comparison with less stable forms of the same medicinal product and, accordingly, to achieve significant advantages over them.

Accordingly, the task of the invention was to obtain a new, stable form of telmisartan, which would satisfy the above-mentioned high requirements for the active substance of the dosage form.

When creating the invention, it was unexpectedly established that telmisartan can be obtained in the form of its 65 sodium salt of formula 1

(0

Me

I dog Y e Di

M M

70 g and about Ying! in crystalline form. Due to the appropriate choice of conditions, it is possible to selectively obtain the 20th polymorphic form of the crystalline sodium salt that meets the above requirements.

One of the distinguishing features of this crystalline form of telmisartan sodium is its melting point

T, equal to 245-592 (when determined using differential scanning calorimetry (DSC) at a heating rate of 10OK/min). Accordingly, the present invention relates to the crystalline sodium salt of telmisartan, which is distinguished by the fact that its melting temperature T is 245-5 C (when determined according to p. 25 using DSC). The indicated value was determined using the 05С821 system of the Mesheg-Toiedo company. Go)

In more detail, the crystalline form of the sodium salt of telmisartan proposed in the invention was studied using spectroscopy. The powder X-ray pattern obtained during these studies is presented in the drawing attached to the description. Table 1 shows the spectroscopic analysis data below. Бк со со сч 35 со вв ва! 8000 MeV! yes « yu showed 00035000 wav 00008 - - tt 0110000 tav 11109

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In the given table, the index "29 |) means the diffraction angle in degrees, and the index "Y(E)" means the determined interplanar distances in the crystal lattice in E.

According to the data presented in the table, this invention relates to the crystalline sodium salt (F) of telmisartan, which is distinguished by the fact that its powder X-ray pattern, along with others, has characteristic values of interplanar distances 4, which are 20.95E, 17.72E, 13.97E and 13.63E.

According to the invention, powder radiographs were registered using the VgyKkeg U8 Admapsead system, which is equipped with a DLC (detector with local sensitivity) (Si-Co radiation, 5.-1.5418E, ЗОкВ, 40mA).

The present invention also relates to the crystalline sodium salt of telmisartan proposed therein in the form of its solvates and hydrates, preferably in the form of its hydrates and particularly preferably in the form of its hemihydrate.

Another object of this invention is a method of obtaining the crystalline sodium salt of telmisartan proposed therein. Telmisartan 65 can be used as a starting material for the preparation of this crystalline sodium salt of telmisartan in the form of a free acid, which can be obtained by methods known in the art

For example, according to ER 502314 AT).

To obtain the crystalline sodium salt proposed in the invention, telmisartan in the form of a free acid is dissolved in a suitable solvent, preferably in an organic aprotic solvent, especially preferably in an organic aprotic and non-polar solvent. Solvents particularly preferred according to the invention are toluene, chloroform, dichloromethane, tetrahydrofuran, diethyl ether, diisopropyl ether, methyl tert-butyl ether, acetone, methyl isobutyl ketone, benzene or acetonitrile, the most preferred of which are toluene, benzene and methyl isobutyl ketone. The most preferred solvent according to the invention is toluene.

Per gram of telmisartan (free acid) it is preferable to use from 0.5 to ml, more preferably from 1 to

Zml, especially preferably from 1.5 to 2.5 ml solvents from the list mentioned above. 70 Then the corresponding sodium salt is added to the resulting solution or suspension as a basis. Sodium salts suitable for this purpose are, according to the invention, sodium hydroxide, sodium hydride, sodium carbonate, sodium hydrogencarbonate or sodium alcoholates. By sodium alcoholates in the context of this description is meant the sodium salts that are formed with lower alcohols, preferably with alcohols selected from the group consisting of methanol, ethanol, isopropanol, n-propanol, tert-butanol, sec-butanol, isobutanol, n -butanol and tert-amyl /5 bpyrt. Of greatest interest according to the invention are sodium salts selected from the group that includes sodium hydroxide, sodium hydride, sodium ethanolate and sodium methanolate, while the most preferred according to the invention are sodium hydroxide and sodium methanolate. The above-mentioned sodium salts can be added to the reaction mixture in the form of solids. However, in the case of sodium hydroxide, it is advisable to add it in the form of aqueous solutions. It is especially preferable to use concentrated aqueous solutions of 2% sodium hydroxide. So, in particular, caustic sodium can be used for these purposes in a concentration of about 45% by weight.

The amount of sodium salt used depends, as is obvious, on the amount of free acid telmisartan used. According to the invention, it is intended to add at least 1 mol of sodium salt per mol of telmisartan. At the same time, it is also possible to add sodium salt in excess. with

It is preferable to add from 1 to 2.5, more preferably from 1 to 2, especially preferably from 1 to 1.5 moles of sodium salt per mole of telmisartan used in the form of acid. (at)

When using sodium hydroxide as a sodium salt and adding it in accordance with one of the preferred embodiments of the method proposed in the invention in the form of aqueous solutions, it may be appropriate to add an organic solvent that is miscible with water. Such a solvent can be selected from the group consisting of methanol, ethanol, isopropanol, acetone, tetrahydrofuran, tert-butane, 2-butanol, butanol, glycol, ethyl diglycol, 1,3-butanediol, 1,4-butanediol, tert-amyl alcohol, acetonitrile, nitromethane, formamide, dimethylformamide, M-methylpyrrolidone, dimethylsulfoxide, dimethylacetamide, nitroethane, and methoxy-2-propanol, with the aforementioned alcohols being given special importance. It is particularly preferable to use methanol or ethanol in the implementation of the method proposed in the invention, of which ethanol is more preferred. On mole According to the invention, it is preferable to use from 50 to 500 ml, especially preferably from 100 to 400 ml, most preferably from 200 to 350 ml of this solvent. Then the reaction mixture can be heated, thus accelerating the further course of the reaction. The reaction mixture is preferably heated with thorough stirring to a temperature above 402C, especially preferably above 602C. The choice of the maximum heating temperature is determined, as is obvious, by the boiling point of the used solvent. If "

According to the invention, in the above-mentioned variants of its implementation, solvents are used from among the predominant ones, so it is advisable to heat to a temperature above 7029C. The duration of this heating is, as a rule, from 15 minutes to 2 hours, preferably from 20 minutes to one hour. After that, the resulting solution is filtered and the residue of the solid substance on the filter (if present) is washed with one or more solvents from the list mentioned above.

To an organic solvent heated to a temperature above 402C, preferably above 602C, especially preferably

Go | to its boiling temperature, slowly, preferably drop by drop, add the filtrate obtained by the method described above. As a solvent in the considered case, it is preferable to use an organic aprotic solvent, and especially preferably an organic aprotic and non-polar solvent. According to the invention, the most preferred solvents include such solvents as toluene, chloroform, dichloromethane, tetrahydrofuran, diethyl ether, diisopropyl ether, methyl tert-butyl ether, acetone, methyl isobutyl ketone, benzene and acetonitrile, the most preferred of which are toluene, benzene and methyl isobutyl ketone. A particularly preferred solvent is, according to (according to the invention, toluene. At the same time, in the process of adding the filtrate to the pre-loaded heated solvent, according to one of the preferred variants of the method, part of the solvent is distilled off (optionally by azeotropic distillation). After the addition process is completed, if necessary, it is removed by distillation the remaining part of the solvent (for example, on the order of 1 to 2 thirds of the total amount of solvent used up to that point). in the form of crystals. After the completion of crystallization, the crystals are separated, if necessary, washed with the aforementioned organic solvent and then dried. 60 According to another embodiment of the invention, the crystalline sodium salt of telmisartan proposed in it is obtained on the basis of the acid-addition salts of the formula 2 b5 and x " M

Y Phi 2 ( p 7 o (ze) (ze) (ge) p

Zoso where H-X means an acid selected from the group consisting of hydrochloric acid, hydrobromic acid, toluenesulfonic acid and methanesulfonic acid. The most important of the acid addition salts of formula 2 is the salt in which H-X stands for hydrochloric acid. Further in the description, this acid addition salt is also referred to as telmisartan hydrochloride. "from the compound of formula 2 it is possible to obtain, for example, from the tert-butyl ether known in the state of the art 4-(2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazol-1-ylImethyl|biphenyl-2 -carboxylic acid (ie tert-butyl ether of telmisartan) by saponification in acetic acid in the presence of H-X acid.

The crystalline sodium salt of telmisartan of formula 1 proposed in the invention can be obtained according to the invention starting from the acid addition salts of formula 2 in the following way. of the compound of formula 2 is dissolved in the appropriate solvent and mixed with the appropriate sodium salt. As a solvent, water and/or a suitable alcohol, such as methanol, ethanol or isopropanol, mixed with a co-aprotic organic solvent selected from the group consisting of toluene, chloroform, dichloromethane, c 20 tetrahydrofuran, diethyl ether, diisopropyl ether, methyl- tert-butyl ether, acetone, methyl isobutyl ketone, benzene and acetonitrile. It is particularly preferred to use as a solvent water in a mixture with bo» ethanol or isopropanol in a mixture with an aprotic organic solvent selected from the group which includes toluene, benzene and methyl isobutyl ketone, the most preferred of which is toluene. The mixture of water, isopropanol, and toluene turned out to be especially preferable in the implementation of this stage of synthesis. 29 The amount of the used solvent, the correspondingly used mixture of solvents depends on the amount of the used acid-addition salt of formula 2. It is preferable to use approximately 0.3-3.5 l per mole of the compound of formula 2 used, more preferably approximately 1-2.5 l, especially preferably approximately 1.5-2 liters of solvent, respectively, a mixture of solvents from among the aforementioned. If the preferred solvent mixture according to the invention is used as a solvent, which together with water and an aprotic organic solvent contains some alcohol as a third component, then the volume ratio between water and aprotic organic solvent should be, according to the invention, preferably from 1: 5 to 1:50, and the volume ratio between water and alcohol used should be from 2:1 to 1:40. In such a mixture of solvents, the following ratios are preferred: between water and aprotic organic solvent - in the range from 1:10 to 1:30, more preferably from 1:15 to 1:25, and between water and the alcohol used - in the range from 1:11 to bo 1:20, more preferably from 1:5 to 1:15.

Per mole of the compound of formula 2, the above-mentioned solvent, respectively, the mixture of solvents preferably contains from about 10 to 100 ml, preferably from about 30 to 80 ml, especially preferably from about 40 to 70 ml of water. In addition, the used solvent, respectively, the mixture of solvents per mole of the compound of formula 2 preferably contains from about 100 to 1000 ml, more preferably from about 300 to 800 ml, especially preferably from about 400 to 7000 ml of alcohol. As the third component, the used solvent, respectively, the mixture of solvents per mole of the compound of formula 2 contains preferably from about 200 to 2000 ml, more preferably from about 600 to 1b600 ml, especially preferably from about 800 to 1400 ml of the above-mentioned aprotic organic solvent. 70 Sodium hydroxide, sodium hydride, sodium carbonate, sodium hydrogencarbonate or sodium alcoholates can be used as sodium salts suitable for converting compounds of formula 2 into compounds of formula 1. By sodium alcoholates is meant the sodium salts formed with lower alcohols, preferably with alcohols selected from the group consisting of methanol, ethanol, isopropanol, n-propanol, tert-butanol, sec-butanop, isobutanol, n-butanol and tert - amyl alcohol. Of particular interest according to the invention /5 are sodium salts selected from the group that includes sodium hydroxide, sodium hydride, sodium ethanolate and sodium methanolate, while for this stage of the reaction, the most important importance according to the invention are such sodium alcoholates as sodium ethanolate and sodium methoxide, primarily sodium methoxide. The above sodium salts can be added to the reaction mixture in the form of solids. However, in the case of sodium methanolate, it is advisable to add it in the form of methanolic solutions. At the same time, especially preferably

Use such methanol solutions of sodium methanolate, which contain it in a concentration of at least 10905, especially preferably of the order of 20-4095 (volume/volume). So, for example, a methanolic solution of sodium methanolate can be used with a concentration of the order of ZOmass.9o.

The amount of sodium salt used depends, as is obvious, on the amount of free acid telmisartan used. According to the invention, at least 2 moles of the sodium salt must be added per mole of the used acid-additive salt of telmisartan of formula 2. It is equally possible to add sodium salt in excess. (at)

Under certain conditions, it may be appropriate to add activated carbon to the above reaction mixture.

So, in particular, activated carbon can be added in the order of 5-50 g, preferably in the order of 10-40 g, per mole of the sodium salt of formula 2 used. After the addition of the sodium salt and the addition of activated carbon (if any) are completed, the resulting reaction mixture is heated to a temperature in the range of 50 to 50 1002C, preferably from 60 to 902C, especially preferably to a temperature of the order of 70-8020. During this heating, part of the solvent, preferably about 10-5095, especially preferably about 20-4095 of its total amount, can be driven off. with

The remaining suspension is then filtered, the residue on the filter, if necessary, is washed with one of the above-mentioned aprotic organic solvents, preferably the same aprotic organic solvent that is used in the reaction. After that, the resulting filtrate is diluted with a suitable solvent or a mixture of solvents. For these purposes, it is preferable to use a mixture of water and an aprotic organic solvent from among the aforementioned. It is advisable to use approximately 10-100ml, preferably 30-8Oml, especially preferably 40-70ml of water per mole of the starting compound of formula 2 in c. As for the aprotic organic solvent, in the considered case, per mole of the starting compound of formula 2, it is expedient to use it in an amount from 250 to 300 Oml, preferably from approximately 800 to 2000 ml, especially preferably in the order of 1200-180 Oml.

After dilution, the resulting mixture is heated to the distillation temperature. At the same time, approximately 1-2 liters, preferably approximately 1200-1800 ml of solvent are distilled off per mole of the starting compound of formula 2. After distillation of the solvent, the sodium salt of telmisartan of formula 1 proposed in the invention falls out in the form of crystals. The resulting crystals are isolated, if necessary, washed with one of the above-mentioned aprotic organic solvents and

Go! finish drying.

Another object of this invention is the crystalline sodium salt of telmisartan, under certain conditions in the form of its osolvates or hydrates, preferably in the form of its hydrates, especially preferably in the form of its hemihydrate, which is obtained by the above-described method.

Taking into account the main role played by compounds of formula 2 as valuable starting materials in the direct synthesis of the sodium salt of telmisartan of formula 1 proposed in the invention, another object of this invention is compounds of formula 2 as such

F) ko 60 b5 y x " M

Y Phi 2 ( p 7 o (ze) (ze) (ge) p

Zoso where H-X means an acid selected from the group consisting of hydrochloric acid, hydrobromic acid, toluenesulfonic acid and methanesulfonic acid. Particularly preferred is the compound of formula 2, in which H-X means hydrogen chloride, which is telmisartan hydrochloride. First of all, this invention relates to the above-mentioned compounds of formula 2 in crystalline form. "with taking into account the pharmaceutical effectiveness of the crystalline sodium salt of telmisartan sodium salt proposed in the invention, this invention also relates to its use as a medicinal product.

Another object of this invention, taking into account the pharmaceutical effectiveness of the crystalline sodium salt of telmisartan proposed in it, is its use for the preparation of a suitable medicinal product, primarily a medicinal product intended for the prevention or treatment of diseases in which, upon introduction into the body, it is therapeutic active doses of one or more angiotensin I antagonists can provide the necessary therapeutic effect. The present invention relates primarily to the use of the crystalline sodium salt of telmisartan for the preparation of a medicinal product intended for the prevention or treatment of 20 diseases from the group that includes hypertension, heart failure, impaired local blood circulation, cardiac ischemia (angina), further development of heart failure after myocardial infarction , diabetic neuropathy, glaucoma, diseases of the gastrointestinal tract and diseases of the urinary bladder, but mainly intended for the prevention and treatment of hypertension.

Accordingly, another object of this invention is pharmaceutical compositions, which differ in that they contain the crystalline sodium salt of telmisartan. o The synthesis example presented below only illustrates one of the possibilities of the method of obtaining the crystalline sodium salt of telmisartan, without limiting the scope of the invention. Synthesis Example 1: Preparation of the crystalline sodium salt of telmisartan starting from telmisartan

As a starting material for obtaining the crystalline sodium salt of telmisartan 60 proposed in the invention, telmisartan can serve as a free acid, which can be obtained by methods known from the state of the art

See, for example, application ER 502314 AT).

154.4 g of telmisartan in 308.8 ml of toluene are previously placed in a suitable reaction vessel. This suspension is mixed with 27.8 g of 44.6895 sodium caustic and 84.9 ml of ethanol and heated to 782C for about 30 minutes, after which the mixture is filtered. If significant amounts of solids remain on the filter, they should be washed with a mixture of 61.8 ml of toluene and 15.3 ml of ethanol.

Simultaneously with this operation, 463.2 ml of toluene are loaded into another reaction vessel and heated to the distillation temperature. Then, at this temperature, the filtrate obtained by the method described above is slowly added dropwise and azeotropic distillation is carried out at the same time. After completion of the addition process, in the presence of the solution formed as a result of washing the filtrate, this solution can also be added, also carrying out azeotropic distillation. Distillation is carried out until reaching 103 29 and then the suspension is allowed to cool to room temperature. The precipitated crystals are separated by vacuum filtration, washed with 154.4 ml of toluene and finally dried at 602C in a chamber dryer with air circulation.

Yield: 154.6g (96905) of colorless crystals.

C33NhoM4OoMaho,5Nho: solution: st2.5B1 NoBt2 M 10.25 found: C 72.57 NN 569 M 10.21

Synthesis example 2: Preparation of the crystalline sodium salt of telmisartan starting from telmisartan hydrochloride

A) Preparation of telmisartan hydrochloride 411g of 4-(2-n-propyl-d-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazol-1-yl)methyl|biphenyl-2-carboxylic acid 2o tert-butyl ether is suspended in 822 ml of glacial acetic acid and mixed with 213g of concentrated aqueous hydrochloric acid (3790).This mixture is then heated to the distillation temperature and distilled off with approximately b40ml of solvent.

The formed residue at 50-60 is slowly mixed with about 620 ml of water. Next, 20 g of activated carbon (for example, Moghii ZX 2 OKha) is added to this mixture and the resulting mixture is stirred at a constant temperature for about 10 minutes. After filtering, the residue is washed three times with glacial acetic acid in portions of 25 ml and approximately 6–20 ml of water. The resulting filtrate is again heated to a temperature of the order of 50-602C and mixed with approximately 2 liters of water. After about 12 hours of stirring at a temperature of the order of 232C, the formed crystals are separated by vacuum filtration and washed twice with about 500ml of water and once with about 90Oml of acetone and finally dried at a temperature of the order of 6020.

Yield: 367g (92.5905) of colorless crystals from food. 27896. "Oh

B) Preparation of crystalline sodium salt of telmisartan from telmisartan hydrochloride 55.1 g of telmisartan hydrochloride is dissolved in 110.2 ml of toluene, 5.5 ml of water and 55.1 ml of isopropanol and this mixture is mixed with 36.9 g of sodium methylate (3095 in methanol) and 2.75 g of activated carbon (for example, Zoi 5X 2 OCha). Then the mixture is heated to about 75922 and at a constant temperature for about 30 minutes, about B5Oml of the solvent mixture is distilled off. The obtained suspension is filtered and the residue is washed with approximately 20 ml of toluene. The filtrate is mixed with approximately 5 ml of water and 150 ml of toluene. The resulting mixture is heated to 89°C with a reflux condenser, at the same time driving off by azeotropic distillation approximately 1500 ml of the solvent mixture (at a temperature of the order of 1022°C). Then for one hour at 10023 let the crystals fall out.

These crystals are separated by vacuum filtration, washed with approximately 500 ml of toluene and finally dried at 6026.s 10. Yield: 53.6 g (9995) of colorless crystals. o) : » С33НгоМ4ОоМахо,5Нго: solution: st2.5Б1 НоБт2 М 10.25 found.: С 72.4 НнН5бвв М 1020 (ог) A medicinal product that contains an active substance, primarily a medicinal product for oral use,

F is especially preferably tablets, can be obtained by methods known from the state of the art. Thus, for example, suitable tablets can be made by mixing the active substance or active substances with known excipients, for example with inert diluents such as calcium carbonate, calcium phosphate c 20 or milk sugar, with disintegrants such as corn starch or alginic acid, with binders such as starch or gelatin, with lubricants such as magnesium stearate or talc, and/or with

These means that provide a depot effect, such as carboxymethyl cellulose, cellulose acetophthalate or polyvinyl acetate. Tablets can also consist of several layers.

Some examples of pharmaceutical compositions used according to the invention are presented below. These 22 examples serve only to explain the invention in more detail without limiting its scope. o m bo bo y o y pd s o

Claims (1)

The formula of the invention Y. Crystalline sodium salt of telmisartan of formula 1: Me " ей М Me со Me SD со ІЧ ІІіі 0-00 Мах са ШІІ « which differs in that its melting temperature T is 24555960. 8 s 2. Crystalline sodium salt of telmisartan according to claim 1, which is distinguished by the fact that the following characteristic values of the interplanar distance a are present on its powder X-ray pattern h along with others: 20.95 A, 17.72 A, 13.97 A and 13.63 A. -» 3. Solvate, hydrate or hemihydrate of the crystalline sodium salt of telmisartan according to claim 1 or 2. 4. The method of obtaining the crystalline sodium salt of telmisartan of formula 1, which is characterized by the fact that telmisartan in the form of a free acid is dissolved in a suitable solvent, then this solution is mixed with the corresponding sodium salt, while at least 1 mol of sodium salt is added per mole of telmisartan, then with the reaction mixture is heated for a period of time ranging from 15 min. up to 2 h., after that the resulting solution is filtered and the filtrate obtained in this way is slowly added to an organic solvent heated to a temperature (se) of more than 40 °C, while part of the solvent is optionally distilled off already during the 20 s addition of the indicated filtrate, then the obtained in this way, the concentrated solution is cooled and the sodium salt of telmisartan, which falls out in the form of crystals, is isolated and finally, if necessary, after washing with the above-mentioned organic solvent, it is dried. 5. The method of obtaining the crystalline salt of telmisartan of the formula 1, which is characterized by the fact that the acid-addition salt of the formula 2 Me 2 (F) Metyu me, SD E MI x NACH A b5 where H-X means an acid selected from the group that includes hydrochloric acid, hydrobromic acid, toluenesulfonic acid and methanesulfonic acid are dissolved in the appropriate solvent and subjected to interaction with the appropriate sodium salt, while at least 2 moles of sodium salt are used per mole of the compound of formula 2 used. 6. Crystalline sodium salt of telmisartan, which is obtained by the method according to claim 4 or 5. 7. Use of the crystalline sodium salt of telmisartan according to any of claims 1-3, b as a medicinal product. 8. Pharmaceutical composition, which is characterized by the fact that it contains the crystalline sodium salt of telmisartan according to any of claims 1-3, 6. 9. Compounds of the formula 2 76 Me 2 m Me ve c SD E MI x NACH Y o LOon MI else where H-X means toluenesulfonic acid and methanesulfonic acid. 10. The compound according to claim 9, which is characterized by the fact that it is presented in crystalline form. s 7 o (ze) (ze) (ge) s Zo so - with . and? so ko so o Se ko 60 b5