New Oral Drug Forms Field of the invention The invention relates to novel oral drug forms. The novel drug forms are used in treating stomach and/or intestinal diseases caused by Helicobacter bacteria.
Prior art Many patent applications and granted patents describe pyridylmethylsulphinyl-1H- The following patent applications and granted patents can be mentioned in thecontext benzimidazoles, which have gastric acid secretion inhibiting properties. of the present invention: European patent EP-A-,0 ‘I34 400 (= United States patent US—A-4 555 518), EP-A-0127 763 (= US-A-4 560 693), EP-B-0 166 287(= US-A-4 758 579), EP-A-0 201 575 (=US-A-4 686 230), M089/05299 International patent application W0-A-089/11479. In European patent application EP-A-O 382 489, the suitability of certain pyridylmethylsulphinyl-1H-benzimidazoles - ~ the benzimidazole portion of which is optionally substituted with methoxy or trifluoromethyl is indicated, described and claimed for the treatment of infectious diseases caused by bacteria from the Campylobacter (= Helicobacter) strain.
International patent application W090/09175 discloses the use of omeprazol in the treatment of infectious diseases, in particular those caused by Campylobacter low stability and pyridylmethylsulphinyl-1H—benzimidazoIe, a number of patent applications (for example EP-A-0 244 380 and EP-A-0 247 983) indicate the need to use these active ingredients in a gastric acid resistant form for oral administration. Similarly, pylori. Because of the ready acid degradation of EP-A-0 382 489 cited above employs an enteric-coated formulation when administered orally to control Campylobacter.
Description of the invention The invention concerns the use of 5-difluoromethoxy[(3,4-dimethoxy—2— pyridyl)methyIsu|phiny|]—1H-benzimidazole and its pharmacologically acceptable salts for the manufacture of medicaments for oral administration to control Helicobacter bacteria.
Preferred salts are pharmacologically acceptable basic salts, in particular pharmacologically acceptable salts with the normal inorganic and organic ‘bases used in galenical forms. Examples of basic salts that can be mentioned are lithium, sodium, potassium, calcium, aluminium, magnesium, titanium, ammonium or guanidinium salts.
A particular strain of Helicobacter that can be mentioned is Helicobacter pylori.
Examples of drug forms for oral administration are tablets, coated tablets, hard and soft capsules, produced from gelatine, for example, dispersible powder, granules, aqueous and oily suspensions, emulsions, solutions or syrups; tablets, coated tablets, capsules and granules are advantageously produced to dissolve readily in gastric acid to release the active ingredient into the stomach.
For the purposes of combined treatment of stomach diseases, which are caused by raised gastric acid secretion and damage to the stomach by Helicobacter pylori, drug formulations for oral administration which can be mentioned are those containing the active ingredient in both a gastric acid resistant form and in a non gastric acid resistant form in a single dose. Examples that can be cited are tablets that contain the active ingredient both in a gastric acid resistant core and in a non gastric acid resistant shell, or capsules filled with gastric acid resistant and non gastric acid resistant pellets or (mini) tablets.
In general, in human medicine, the active ingredient is administered in a daily dose of about 0.05 to about 5, preferably 0.1 to 2.5 mg/kg of body work, if necessary in the form of several, preferably 2 to 6 individual doses to achieve the desired result.
Surprisingly, it has been discovered that the compound 5—difluoromethoxy'["(3,4- dimethoxypyridyl)methylsulphinyl]-1H-benzimidazole is much more effective against Helicobacter bacteria in an acid medium than in a neutral medium, and as a result — in contrast to the teaching of the prior art — does not need to be administered in a gastric acid resistant form.
Thus, the invention concerns the use of 5—difluoromethoxy[(3,4-dimethoxy pyridyl)methy|su|phinyI]—1H—benzimidazole and its pharmacologically acceptable salts for the preparation of medicaments which are in a formulation which is V resistant to gastric acid for oral administration to control Helicobacter bacteria.
The compound 5—dif|uoromethoxy[(3,4-dimethoxypyridyl)methylsulphinyI]-1H- benzimidazole and its pharmacologically acceptable salts is known from Drugs for oral administration using active ingredients with formula l are manufactured in a manner that is well known to the skilled person.