HRP921400A2 - Substituted benzimidazoles, process for their preparation as well as their use - Google Patents

Description

Field of invention

The aim of the present invention is to provide new compounds which prevent exogenous simulated gastric acid secretion and thus can be used in the prevention and treatment of gastric ulcer.

The present invention also relates to the use of the compounds of the invention for inhibiting gastric acid secretion in mammals including humans. In a general sense, the compounds of the invention can be used to prevent and treat gastrointestinal inflammatory diseases, and gastric acid-related diseases in mammals, including humans, such as gastritis, gastric ulcer, duodenal ulcer, reflux esophagitis, and Zollinge-Ellison 's syndrome. Furthermore, the compounds can be used for the treatment of other gastrointestinal disorders in which a gastric antisecretory effect is desired, eg in patients with gastrinomas, and in patients with acute upper gastrointestinal bleeding. They may also be used in patients in intensive care situations, both pre- and post-operatively to prevent acid aspiration and stress for the treatment or prophylaxis of inflammatory diseases in mammals, including humans, particularly those involving lysosomal enzymes. Conditions that can be specifically mentioned are rheumatoid arthritis and gout. The invention also relates to pharmaceutical preparations containing the compounds of the invention as an active ingredient. In another aspect, the invention relates to processes for the preparation of such new compounds and to the use of active compounds for the preparation of pharmaceutical preparations for medical use indicated above.

The compounds of the invention will not block iodine consumption by the thyroid gland. Earlier, several lectures from the company, where the inventors worked, described that thyroid toxicity depends on whether the compounds are lipophilic or not. The inventors have now unexpectedly found that lipophilicity is not a critical parameter. The protected compounds, which include quite hydrophilic compounds, do not have any harmful effect on the thyroid gland, and at the same time have a high inhibitory effect on the secretion of gastric acid.

The compounds of the invention will also exhibit high solubility and high chemical stability in water.

The basis of the invention

Similar disubstituted 2-(((3,4-dialkoxy-2-pyridinyl)-methyl)-sulfinyl)-1Hbenzimidazol-1-yl compounds are described in PCT/SE91/90415, but this patent was not publicly available at the time of the original filing. applications in Sweden, it was already published a little later.

Earlier technique

Benzimidazole derivatives intended for preventing gastric acid secretion are described in numerous patent documents.

Among these may be mentioned GB 1 500 043, GB 1 525 958, US 4 182 766, US 4 255 431, US 4 599 349, BE 898 880, EP 124 495, EP 208 452, EP 221 041, EP 279 149, EP 176 308 and Derwent Abstract 87-294449/42. Benzimidazole derivatives proposed for the treatment or prevention of specific gastrointestinal inflammatory diseases are described in US 4,359,465.

Invention

The compounds of the invention are effective as inhibitors of gastric acid secretion in mammals, including humans, and in addition do not block iodine consumption in the thyroid gland.

Furthermore, the compounds of the invention exhibit high solubility and high chemical stability in water.

The compounds of the invention are therefore particularly suitable for parenteral, especially intravenous or intramuscular administration. High solubility and chemical stability also make the compounds of the invention suitable for other routes of administration, such as oral and rectal administration.

The compounds of the invention are of the following formula I:

[image]

where:

R 1 and R 2 , which are different, is each metal, -C(O)-CH 3 or -C(O)-OCH 3 , and wherein one of R 1 or R 2 is always a metal and M is a physiologically acceptable counter cation.

The structural isomers of the compounds of formula I can be used separately, or in equal or unequal mixtures.

The compounds of the invention of formula I have an asymmetric center in the sulfur atom, i.e. they exist as two optical isomers (enantiomers). Both pure enantiomers, racemic directions (50% of each enantiomer) and unequal mixtures of the two are within the scope of the present invention.

It is believed that the compounds of formula I are metabolized before exerting their effect. Such metabolism occurs in the N-substituent, a phosphorus-containing group, in position 1 of the benzimidazole nucleus.

Fixing

The compounds of the invention can be made according to the following procedures:

a) By the reaction of the compound of formula II:

[image]

wherein R1 and R2 are as defined under formula I, and Z is such a halogen as Cl, Br or J or a functionally equivalent group thereof, with a compound of formula III:

[image]

in which Q is a counter ion such as Na+, K+, Ag+ or trialkylammonium.

The resulting salts can be transformed into a therapeutically suitable salt, such as sodium or potassium salts, by addition of NaOH or KOH, or by ion exchange.

b) By oxidation of the compound of formula IV:

[image]

wherein R 1 , R 2 and M have the given meanings, so that a compound of formula I is obtained.

This oxidation can be carried out using such an oxidizing agent as nitric acid, hydrogen peroxide (optionally in the presence of vanadium compounds), peracids, peresters, ozone, dinitrogen tetraoxide, iodosobenzene, N-halosuccinimide, 1-chlorobenzotriazole, t-butyl hypochlorite, diazabicyclo (2,2 ,2)-octane bromine complex, sodium metaperiodate, selenium dioxide, manganese dioxide, chromic acid, cerium ammonium nitrate, bromine, chlorine and sulfuryl chloride. Oxidation is usually carried out in such a solvent as halogenated hydrocarbons, alcohols, ethers, ketones.

Oxidation can also be done enzymatically using an oxidizing enzyme or microbiologically using a suitable microorganism.

The resulting structural isomers can be separated by crystallization or chromatography.

The obtained racemates can be separated according to known procedures, for example by recrystallization from an optically active solvent.

For clinical use, the compounds of the invention are formulated into pharmaceutical formulations for oral, rectal, parenteral or other administration. It is particularly preferred that the compound of the invention is formulated into pharmaceutical formulations for parenteral administration. The pharmaceutical formulation contains the compound of the invention in combination with a pharmaceutically acceptable carrier. The carrier may be in the form of a solid, semi-solid or liquid diluent or capsule. These pharmaceutical preparations are a further object of the invention. Usually, the amount of active compounds is between 0.1-95% by weight. of the preparation, between 0.2-20% wt. in preparations for parenteral use and between 1 and 50% wt. in preparations for oral administration.

In the preparation of pharmaceutical formulations containing a compound of the present invention in the form of dosage units for oral administration, the selected compound can be mixed with a solid, powdered carrier such as lactose, sucrose, sorbitol, mannitol, starch, amylopectin, cellulose derivatives, gelatin or another suitable carrier, as well as with lubricants such as magnesium stearate, calcium stearate, sodium stearyl fumarate and polyethylene glycol waxes. The mixture is then processed into granules or pressed into tablets. Granules and tablets contain sulfoxides, can be coated with an inner coating, which protects the active compound from acid-catalyzed degradation as long as the dosage form remains in the stomach. The inner coating is selected from pharmaceutically acceptable inner coating materials, e.g., beeswax, shellac, or anionic filler-forming polymers, such as cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, partially methyl esterified methacrylic acid polymers, and the like, if desired, in combined with a suitable plasticizer. Different coating colors can be added to this to distinguish tablets or granules with different active compounds or with different amounts of active compound present.

Soft gelatin capsules can be made with capsules containing a mixture of the active compound or compounds of the invention, vegetable oil, fat or other suitable carrier for soft gelatin capsules. Soft gelatin capsules can also be internally coated as described above. Hard gelatin capsules may contain granules or internally coated granules of the active compound. Hard gelatin capsules may also contain the active compound in combination with a solid suspended carrier such as lactose, sucrose, sorbitol, mannitol, potato starch, amylopectin, cellulose derivatives or gelatin. Hard gelatin capsules can be coated internally as described above.

Dosage units for rectal administration can be made in the form of suppositories containing the active substance mixed with a neutral fatty base, or they can be made in the form of a gelatin rectal capsule containing the active substance in a mixture with vegetable oil, paraffin oil or other suitable carrier for gelatin rectal capsules , or they can be made into ready micro-enema form, or they can be made into a dry micro-enema formulation to be reconstituted in some suitable solvent just before administration.

Liquid preparations for oral administration can be made in the form of syrups or suspensions, eg solutions or suspensions containing from 0.2% to 20% by weight. of the active ingredient and the rest contains sugar or sugar alcohols and a mixture of ethanol, water, glycerol, propylene glycol and polyethylene glycol. If desired, such liquid preparations may contain coloring agents, flavoring agents, saccharin and carboxymethylcellulose or other thickening agents. A liquid preparation for oral administration may also be made into a dry powder form for reconstitution with some suitable solvent prior to use.

Solutions for parenteral administration can be made as a solution of the compound of the invention in a pharmaceutically acceptable solvent, preferably in a concentration of 0.1% to 10% by weight. These solutions may also contain solubilizing and/or buffering agents and may be produced as ampoules or vials with various dosage units. Solutions for parenteral administration may also be made up as dry preparations for reconstitution with some suitable carrier immediately before administration.

A typical daily dose of the active substance varies within a wide range and will depend on various factors such as, for example, the individual needs of each patient, the method of administration and the disease. Basically, oral and parenteral doses will be in the range of 5 to 500 mg of active substance per day.

The invention is illustrated by the following examples.

Example 1.

Preparation of phosphoric acid 5-acetyl-6-methyl-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazol-1-yl) methyl ester, disodium salt or phosphoric acid, (6- acetyl-5-methyl-2-(((3,4-dimethoxy-2-pyridinyl)-methyl)-sulfinyl)-1H-benzimidazol-1-yl)methyl ester, disodium salt

Tributylamine (1.7 ml, mmol) was added with stirring to a solution of phosphoric acid, 85% (0.24 ml, 3.6 mmol) in ethanol (2 ml). The solvent was evaporated and the residue was taken up in methylene chloride (2.5 ml). The organic phase is dried over sodium sulfate, filtered and evaporated. 5-acetyl-chloromethyl-6-methyl-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazole or 6-acetyl-1-chloromethyl-5-methyl-2-(( (3,4-Dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazole (0.12 g, 0.28 mmol) and the phosphoric acid tributylammonium salt, made above, were dissolved in methylene chloride (16 mL). Methylene chloride is distilled off and the residue is heated on a water bath for 5 minutes at 60ºC. This procedure is repeated 4 times until the reaction is complete. The residue was dissolved in methylene chloride (4 ml) and washed with 3 portions (4 ml) of water. Add sodium hydroxide solution (0.2 M) to the organic phase with stirring while carefully controlling the pH of the aqueous layer. The aqueous layer was washed with three portions (4 ml) of methylene chloride and then freeze dried to give 40 mg, 27% of the title compound.

NMR data are given below.

Example 2.

Prepares phosphoric acid (5-carbomethoxy-6-methyl-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfonyl)-1H-benzimidazol-1-yl)methylester, disodium salt or phosphoric acid, (6 -carbomethoxy-5-methyl-2-(((3,4-dimethoxy-2-pyridinyl)methyl)-sulfonyl)-1H-benzimidazol-yl)methyl ester, disodium salt

Tributylamine (1.8 mL, 7.8 mmol) was added with stirring to a solution of phosphoric acid, 85% (0.26 mL, 3.9 mmol) in ethanol (2.5 mL). The solvent was evaporated and the residue was taken up in methylene chloride (3 ml). The organic phase is dried over sodium sulfate, filtered and evaporated. 5-carbomethoxy-1-chloromethyl-6-methyl-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfonyl)-1H-benzimidazole or 6-carbonethoxyl-chloromethyl-5-methyl-2-

(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazole (0.14 g, 0.32 mmol) and the phosphoric acid tributylammonium salt, made above, were dissolved in methylene chloride (6.5 ml) and the methylene chloride was distilled off again. and the oil mixture of the product is heated in a water bath for 5 minutes at 60ºC. This procedure is repeated four times until the reaction is complete. The residue is dissolved in methylene chloride (4 ml) and washed with three (4 ml) portions of water. Add sodium hydroxide solution (0.2 M) to the organic phase with stirring until the pH of the aqueous layer is completely controlled. When the pH in the aqueous phase reaches 9-9.5, the mixture is centrifuged. The aqueous layer was washed with three portions (4 ml) of methylene chloride and then freeze dried to give 11 mg, 6% of the title compound.

NMR data are given below.

Table 1

Protons in water are compared to 4.80.

[image]

Preparation of intermediates

Example I-1

Preparation of 5-acetyl-1-hydroxymethyl-6-methyl-2-(((-3,4-dimethoxy-pyridinyl)methyl)sulfinyl)-1H-benzimidazole or 6-acetyl-1-hydroxymethyl-5-methyl-2- (((-3,4-dimethoxy-pyridinyl)methyl)sulfinyl)-1H-benzimidazole

Aqueous 5 M formaldehyde (5.0 ml, 25 mmol). The solution is shaken for 3 minutes. After separation, the organic solution is dried over Na2SO4 and evaporated under reduced pressure to give a red syrup (1.7 g, 78%). The product consists mainly of one of the structural isomers of the title compound as well as small amounts of starting materials. NMR data are given below.

Example I-2

Preparation of 5-acetyl-1-chloromethyl-6-methyl-2-(((-3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazole or 6-acetyl-1-chloromethyl-5-methyl- 2-(((-3,4-dimethoxy-pyrimidinyl)methyl)-sulfinyl)-1H-benzimidazole

Suspension of 5-acetyl-hydroxymethyl-6-methyl-2-(((-3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazole and 6-acetyl-1-hydroxymethyl-5-methyl-2- (((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazole (1.7g, 4.2mmol) in acetonitrile (40ml) was supercooled to -15ºC. Add thionyl chloride (0.50 g, 4.2 mmol) and triethylamine (0.50 g, 4.2 mmol) dropwise in the given order. The mixture is stirred at room temperature for 5 minutes and then evaporated under reduced pressure. The residue is chromatographed on silica gel (70 g) using a mixture of ethyl acetate and methylene chloride as eluent. The amount of ethyl acetate increases during chromatography. Product 0.14 g (8%) consists mainly of one of the structural isomers.

NMR data are given below.

Example I-3

Preparation of 5-carbomethoxy-1-hydroxymethyl-6-methyl-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazole or 6-carbomethoxy-1-hydroxymethyl-5-methyl-2 -(((-3,4-dimethoxy-pyridinyl)methyl-sulfinyl-1H-benzimidazole

In a solution of 5-carbomethoxy-6-methyl-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfonyl)-1H-benzimidazole or 6-carbomethoxy-1-hydroxymethyl-5-methyl-2-(( (3,4-Dimethoxy-2-pyridinyl)methyl)sulfonyl)-1H-benzimidazole

5 M was added to a solution of 5-carbomethoxy-6-methyl-2-((((3,4-dimethoxy-2-pyridinyl)methyl)sulfonyl)-1H-benzimidazole (0.34 g 0.87 mmol) in methylene chloride (25 ml) aqueous formaldehyde (1.7 ml, 1.5 mmol). The mixture is shaken for 3 minutes. After separation, the organic solution is dried over Na2SO4 and evaporated under reduced pressure, adding red syrup (0.36 g, 100%). The product consists mainly of one of the structural isomers of the title compound as well as small amounts of starting materials. NMR data are given below.

Example I-4

Preparation of 5-carbomethoxy-1-chloromethyl-6-methyl-2--(((3,4-dimethoxy-2-pyridinyl)methyl)sulfonyl)-1H-benzimidazole or 6-carbomethoxy-1-chloromethyl-5-methyl- 2--(((3,4-dimethoxy-2-pyridinyl)methyl)sulfonyl)-1H-benzimidazole

A solution of 5-carbomethoxy-1-hydroxymethyl-6-methyl-2-((((3,4-dimethoxy-2-pyridinyl)methyl)sulfonyl)-1H-benzimidazole and 6-carbomethoxy-1-hydroxymethyl-5-methyl- 2-((((3,4-dimethoxy-2-pyridinyl)methyl)sulfonyl)-1H-benzimidazole (0.36 g, 0.87 mmol) in acetonitrile (20 ml) was cooled sharply to -20ºC. Add dropwise thionyl chloride (0.066 ml, 0.90 mmol) and triethylamine (0.10 g, 1.0 mmol) in the given order. The mixture is stirred at room temperature for 5 minutes and then evaporated under reduced pressure. The residue is chromatographed on silica gel (20 g) using a mixture of ethyl acetate and methylene chloride as eluent. Amount of ethyl acetate and methylene chloride as eluents. The amount of ethyl acetate increases during chromatography. The product 0.16 g (43%) consisted mainly of one of the structural isomers.

NMR data are given below.

Table 2

[image]

Table 3

Examples of compounds included in formula I are given in the following Table.

[image]

The best way of carrying out the invention that is currently known is to use the compound according to example 2.

Pharmaceutical preparations containing the compound of the invention as an active ingredient are illustrated in the following formulations.

SYRUP

The syrup containing 1% (mass by volume) of the active substance is made from the following ingredients:

Compound according to example 1. 1.0 g

Sugar, powder 30.0 g

Saccharin 0.6 g

Glycerol 5.0 g

Flavoring agent 0.05 g

Ethanol 95% 5.0 g

Distilled water q.s. to the final volume of 100 ml

Dissolve sugar and saccharin in 60 g of warm water. After cooling, the active compound is added to the sugar solution and glycerol and a solution of the flavoring agent dissolved in ethanol are added. The mixture is diluted with water to a final volume of 100 ml.

INNER COATED TABLETS

The inner coated tablet containing 20 mg of the active compound is made from the following ingredients:

I Compound mixture according to example 2. 200 g

Lactose 700 g

Methylcellulose 6 g

Cross-linked polyvinylpyrrolidone 50 g

Magnesium stearate 15 g

Sodium carbonate 6 g

Distilled water q.s.

II Cellulose acetate-phthalate 200 g

Cetyl alcohol 15 g

Isopropanol 2,000 g

Methylene chloride 2,000 g

I The compound according to example I, powder, is mixed with lactose and granulated with an aqueous solution of methylcellulose and sodium carbonate. A wet mass is formed through a sieve and the granulate is dried in the oven. After drying, the granulate is mixed with polyvinyl pyrrolidine and magnesium stearate. The dry mixture is pressed into the inner parts of the tablet (10,000 tablets), where each tablet contains 20 mg of the active substance, in a tableting machine that uses punches with a diameter of 6 mm.

II A solution of cellulose acetate-phthalate and cetyl alcohol in isopropanol/methylene chloride is sprayed onto the tablets in an Accela CotaR, Manestry coating equipment. The final weight of the tablet is 110 mg.

SOLUTION FOR INTRAVENOUS ADMINISTRATION

The parenteral formulation for intravenous use, which contains 4 mg of the active compound per ml, is made from the following ingredients:

Compound according to example 2 4 g

Sterile water to a final volume of 1000 ml

The active compound is dissolved in water to a final volume of 1000 ml. The solution is filtered through a 0.22 µm filter and immediately dispensed into sterile 10 ml ampoules. The ampoules are closed.

PILLS

Tablets containing 30 mg of the active compound are made from the following ingredients:

Compound according to example 3 in table 3 300 g

Lactor 700 g

Methylcellulose 6 g

Cross-linked polyvinylpyrrolidone (PVP-XL) 62 g

Disodium acid phosphate 2 g

Magnesium stearate 30 g

Purified water q.s.

The active compound is mixed with lactose and part of PVP-XL and granulated with a solution of methyl cellulose and disodium acid phosphate. The wet mass is forced through a sieve and dried in a fluidized bed dryer. After adding magnesium stearate and sotat to PVP-XL and mixing, the drug mixture is compressed into tablets with an average weight of 110 mg, each tablet containing 30 mg of the active compound.

INNER COATED TABLETS

500 g of the above tablets are coated from the inside. The bottom preparation solution is sprayed onto the tablets in a fluidized bed apparatus using the Wurster coating technique.

Coating solution:

Cellulose acetate-phthalate 40 g

Cetyl alcohol 2 g

Isopropanol 400 g

Dichloromethane 400 g

The final coated tablet had a mass of 117 g.

SUPPOSITORS

Suppositories are made from the following ingredients using a welding process. Each suppository contained 40 mg of the active compound.

Compound mixture according to Example 4 in Table 3 4 g

Witepsol H-15 100 mg

The mixture of the active compound is homogeneously mixed with Witepsol H-15 at a temperature of 41ºC. The melted mass fills the volume of the prefabricated suppository package to a net weight of 1.84 g. After cooling, the packages are closed by heating. Each suppository contained 40 g of the active compound.

Just before use, the active compound dissolved in 10 ml of sterile water is transferred to 100 ml of normal saline for infection so that a total volume of about 110 ml is obtained. The solution is given as an intravenous infusion over a period of about 30 minutes.

SYRUP

The syrup containing 1% of the active substance is made from the following ingredients:

Compound according to example 3 in table 3 1.0 g

Sugar, powder 30.0 g

Saccharin 0.6 g

Flavoring agent 0.05 g

Ethanol 96% 5.0 g

Purified water q.s. up to 100 ml

Dissolve sugar and saccharin in 60 g of warm water. After cooling, the active compound is added to the sugar solution and a solution of fragrances dissolved in ethanol is added. The mixture is diluted with water to a final volume of 100 ml.

SOLUTION FOR INTRAVENOUS OR INTRAMUSCULAR INJECTION

Compound according to example 1 60 g

Water for injections for refilling up to 1000 ml

The active compound is dissolved in water to a final volume of 1000 ml. The solution is filtered through a sterile 0.22 µm filter and aseptically dispensed into sterile ampoules of 1 ml. The ampoules are closed.

FORMULATION FOR INTRAVENOUS INFUSION

Sterile compound according to example 2 60 mg

Vials and closures for sterile injections

Sterile active compound, 60 mg is dispensed into sterile injection vials of 10 ml. Vials are closed with sterile rubber closures. Filling operations are performed under aseptic conditions in a sterile production area under vertical laminar flow.

Witepsol H-15

The mixture of the active compound is homogeneously mixed with Witepsol H-15 at a temperature of 41 ºC. The melted mass fills the volume of the prefabricated suppository package to a net weight of 1.84 g. After cooling, the packages are closed by heating. Each suppository contained 40 g of the active compound.

Just before use, the active compound dissolved in 10 ml of sterile water is transferred to 100 ml of normal saline for infusion so that a total volume of about 110 ml is obtained. The solution is given as an intravenous infusion over a period of about 30 minutes.

SYRUP

The syrup containing 1% of the active substance is made from the following ingredients:

Compound according to example 3 in table 3 1.0 g

Sugar powder 30.0 g

Saccharin 0.6 g

Flavoring agent 0.05 g

Ethanol 96% 5.0 g

Purified water q.s. up to 100 ml

Dissolve sugar and saccharin in 60 g of warm water. After cooling, the active compound is added to the sugar solution and a solution of fragrances dissolved in ethanol is added. The mixture is diluted with water to a final volume of 100 ml.

SOLUTION FOR INTRAVENOUS OR INTRAMUSCULAR INJECTION

Compound according to example 1 60 g

Water for injections for refilling up to 1000 ml

The active compound is dissolved in water to a final volume of 1000 ml. The solution is filtered through a sterile 0.22 µm filter and aseptically dispensed into sterile ampoules of 1 ml. The ampoules are closed.

FORMULATION FOR INTRAVENOUS INFUSION

Sterile compound according to example 2 60 mg

Vials and closures for sterile injections

Sterile active compound, 60 mg is dispensed into sterile injection vials of 10 ml. Vials are closed with sterile rubber closures. Filling operations are performed under aseptic conditions in a sterile production area under vertical laminar flow.

Claims (19)

1. Compounds of formula I: [image] characterized by the fact that in the formula R1 and R2, which are different, are each methyl, -C(O)-CH3 or -C(O)-OCH3 and one of R1 and R2 is always methyl and M is the physiologically acceptable opposite cation. 2. Compound according to claim 1 characterized in that M is Na, K, Ag or trialkylammonium. 3. Compounds according to formula I of claim 1, characterized in that the mixture of phosphoric acid (5-acetyl-6-methyl-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazol-1- yl)-methyl ester, disodium salt and phosphoric acid, (6-acetyl-5-methyl-1-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazol-1-yl)methyl ester, disodium salts. 4. The compound according to formula I of claim 1, characterized in that the mixture of phosphoric acid (5-carbomethoxy-6-methyl-2--(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazole- 1-yl)-methyl ester, disodium salt and phosphoric acid, (6-carbomethoxy-5-methyl-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazol-1-yl) -methyl ester, disodium salt. 5. Compound according to claim 1, characterized in that phosphoric acid 5-acetyl-6-methyl-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazol-1-yl)methylester , disodium salt. 6. Compound according to claim 1, characterized in that phosphoric acid 6-acetyl-5-methyl-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazol-1-yl)methylester , disodium salt. 7. Compound according to claim 1, characterized in that phosphoric acid 5-carbomethoxy-6-methyl-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazol-1-yl)methylester , disodium salt. 8. Compound according to claim 1, characterized in that phosphoric acid 6-carbomethoxy-5-methyl-2-(((3,4-dimethoxy-2-pyridinyl)methyl)sulfinyl)-1H-benzimidazol-1-yl)methylester , disodium salt. 9. Pharmaceutical preparation, characterized in that it contains as an active ingredient the compound according to Claim 1. 10. The compound defined in claim 1, characterized in that it is used in therapy. 11. A compound as defined in claim 1, characterized in that it is used to prevent the secretion of gastric acid in mammals, including humans. 12. A compound as defined in claim 1, characterized in that it is used for the treatment of gastrointestinal diseases in mammals, including humans. 13. A method for preventing the secretion of gastric acid, characterized in that mammals, including humans, are given the compound as defined in claim 1. 14. A method for the treatment of gastrointestinal inflammatory diseases, characterized in that mammals, including humans, are administered the compound as defined in claim 1. 15. Use of the compound according to claim 1 in the production of a drug for preventing the secretion of gastric acid in mammals, including humans. 16. Use of the compound according to claim 1 in the production of a drug for the prevention, treatment of gastrointestinal inflammatory diseases in mammals, including humans. 17. Process for the preparation of the compound of formula I according to claim 1, characterized in that: a) the compound of formula II reacts: [image] wherein R1 and R2 are as defined under formula I and Z is such a halogen as Cl, Br, or J or a functionally equivalent group with a compound of formula III: [image] wherein Q is such a counter ion as Na+, K+, Ag+ or tributylammonium, or b) the compound of formula IV is oxidized: [image] in which R1, R2 and M have the given meanings, so that the compound of formula I is obtained. 18. Compound of formula II: [image] characterized in that R1 and R2 are as defined under formula I and Z is such a halogen as Cl, Br or J or a functionally equivalent group 19. A compound according to Claim 19, characterized in that R1 and R2 are as defined above and Z is Cl or Br.