IL99471A - Pharmaceutical compositions for treating helicobacter bacteria infections containing 5-fluoromethoxy-2-(3,4-dimethoxy-2-pyridyl)methylsulphinyl)-1h-benzimidazole and salts thereof in combination with an antimicrobial agent - Google Patents
Pharmaceutical compositions for treating helicobacter bacteria infections containing 5-fluoromethoxy-2-(3,4-dimethoxy-2-pyridyl)methylsulphinyl)-1h-benzimidazole and salts thereof in combination with an antimicrobial agentInfo
- Publication number
- IL99471A IL99471A IL9947191A IL9947191A IL99471A IL 99471 A IL99471 A IL 99471A IL 9947191 A IL9947191 A IL 9947191A IL 9947191 A IL9947191 A IL 9947191A IL 99471 A IL99471 A IL 99471A
- Authority
- IL
- Israel
- Prior art keywords
- salts
- benzimidazole
- combination
- dimethoxy
- pyridyl
- Prior art date
Links
- 241000589989 Helicobacter Species 0.000 title claims abstract description 11
- 150000003839 salts Chemical class 0.000 title claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 6
- 239000004599 antimicrobial Substances 0.000 title claims description 4
- 208000015181 infectious disease Diseases 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims description 8
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 6
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 6
- 229960003022 amoxicillin Drugs 0.000 claims description 6
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims description 6
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- -1 3 , 4-dimethoxy-2-pYridyl Chemical group 0.000 claims description 3
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 claims description 3
- 229930182566 Gentamicin Natural products 0.000 claims description 3
- 229960003276 erythromycin Drugs 0.000 claims description 3
- PLHJDBGFXBMTGZ-WEVVVXLNSA-N furazolidone Chemical compound O1C([N+](=O)[O-])=CC=C1\C=N\N1C(=O)OCC1 PLHJDBGFXBMTGZ-WEVVVXLNSA-N 0.000 claims description 3
- 229960001625 furazolidone Drugs 0.000 claims description 3
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims description 3
- 229960000282 metronidazole Drugs 0.000 claims description 3
- IAIWVQXQOWNYOU-FPYGCLRLSA-N nitrofural Chemical compound NC(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 IAIWVQXQOWNYOU-FPYGCLRLSA-N 0.000 claims description 3
- NXFQHRVNIOXGAQ-YCRREMRBSA-N nitrofurantoin Chemical compound O1C([N+](=O)[O-])=CC=C1\C=N\N1C(=O)NC(=O)C1 NXFQHRVNIOXGAQ-YCRREMRBSA-N 0.000 claims description 3
- 229960000564 nitrofurantoin Drugs 0.000 claims description 3
- 229960001907 nitrofurazone Drugs 0.000 claims description 3
- 229940056360 penicillin g Drugs 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 241000894006 Bacteria Species 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 210000004051 gastric juice Anatomy 0.000 description 10
- 241000590002 Helicobacter pylori Species 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 229940037467 helicobacter pylori Drugs 0.000 description 5
- 239000002253 acid Substances 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 2
- 241000589876 Campylobacter Species 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- IQPSEEYGBUAQFF-UHFFFAOYSA-N Pantoprazole Chemical compound COC1=CC=NC(CS(=O)C=2NC3=CC=C(OC(F)F)C=C3N=2)=C1OC IQPSEEYGBUAQFF-UHFFFAOYSA-N 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- PKHPZNKXOBWFCX-UHFFFAOYSA-N 2-(4-hydroxy-3-phenylbenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C(C=2C=CC=CC=2)=C1 PKHPZNKXOBWFCX-UHFFFAOYSA-N 0.000 description 1
- YGTUPRIZNBMOFV-UHFFFAOYSA-N 2-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C=C1 YGTUPRIZNBMOFV-UHFFFAOYSA-N 0.000 description 1
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical class NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229950003153 amsonate Drugs 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229950002281 fendizoate Drugs 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 230000027119 gastric acid secretion Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 229950000177 hibenzate Drugs 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229950001506 metembonate Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229960000381 omeprazole Drugs 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- 229960005019 pantoprazole Drugs 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 229940114926 stearate Drugs 0.000 description 1
- 208000018556 stomach disease Diseases 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention concerns the use of compound of formula (I), in which the substituents and symbols are as defined in the specification, against Helicobacter bacteria.
Description
PHARMACEUTICAL COMPOSITIONS FOR TREATING HELICOBACTER BACTERIA, CONTAINING 5-FLU0R0METH0XY-2-((3,4-DIMETH0XY-2-PYRIDYL) METHYLSULPHINYL) -1H-BENZIMIDAZ0LE AND SALTS THEREOF, IN COMBINATION WITH AN ANTIMICROBIAL AGENT 7_.-πρ7η7ϋ:)κ DTU DV WX2 on'n'pm 7iT eTD7TJ3-iH - 1 - 99471/3 Scope of application o ^the invention ί The invention relates to new oral drug forms . The new drug forms are employed for the treatment of diseases of the stomach and/or intestine caused by Helicobacter bacteria.
Pyridylmethylsulphinyl-ia-benzimidazoles which have gastric acid secretion-inhibiting properties are described in a large number of patent applications . The following patent applications and patents may be mentioned in particular here in connection with the present invention: EP-A-134 400 (= IL 71774 ), EP-A-127 763 (= IL 71665 ), EP-B-166 287 (= IL 75400 ), EP-A-201 575 ( = IL 76839. ), WO89/05299 and W089/11479. - European Patent Application ΞΡ-Α-382 489 describes and claims the suitability of certain pyridylmethylsulphinyl-ΙΞ-benzimidazoles , which are substituted in the benzimidazole part, if desired, by methoxy or trifluoromethyl, for the treatment of infectious diseases caused by bacteria of the Campylobacter (= Helicobacter) strain. International Patent Application WO90/09175 discloses the use of omeprazole in the treatment of infectious diseases, in particular those caused by Campylobacter pylori.
Because the pyridylmethylsulphinyl-lH-benzimidazoles have a low stability and are easily decomposed by acid, various patent applications (e.g. IL 82910 o ΞΡ-Α-247 983) refer to the need to administer these active compounds in a form which is resistant to gastric juice in the case of oral administration. An "enteric coated" formulation is also used in the abovementioned EP-A-382 489 as the oral presentation form for combating Campylobacter.
Description of the invention The invention relates to a pharmaceutical composition to be administered orally for combating Helicobacter bacteria comprising as active ingredient a compound - 2 - 99471/ 2 containing 5-difluoro-methoxY-2- [ ( 3 , 4-dimethoxY-2-pyridyl ) -methylsulphinyl]-lH-benzimidazole and/or its pharmacologically tolerated salt, in combination with an antimicrobial agent chosen from the group comprising penicillin G, gentamycin, erythromycin, nitrofurazone, nitrofurantoin, furazolidone, metronidazole and amoxycillin.
A preferred embodiment of the present invention provides a pharmaceutical composition to be administered orally for combatting Helicobacter pylori, containing 5-difluoro-methoxy-2- [ ( 3 , 4-dimethoxy-2-pyridy1 ) -methy1-sulphinyl] -ΙΗ-benzimidazole, in combination with amoxycillin.
The invention also provides a process for the preparation of pharmaceutical preparations which contain one or more compounds as described herein as the active compound and customary excipients, characterized in that the active compound which has been prepared in a known manner is mixed with the customary excipients and the mixture is converted into a medicament to be administered orally for combatting Helicobacter bacteria.
Preferred possible salts for compounds of the present invention are all the pharmacologically tolerated acid addition salts. Salts which may be mentioned in particular are the pharmacologically tolerated salts of the inorganic and organic acids usually used in galenics. Examples of such suitable salts are water-soluble and water-insoluble acid addition salts, such as the hydrochloride, hydrobromide , hydriodide, phosphate, nitrate, sulphate, acetate, citrate, gluconate, benzoate, hibenzate, fendizoate, butyrate, sulphosalicylate, maleate, laurate, malate, fumarate, succinate, oxalate, tartrate, amsonate, - 3 - 99471/2 embonate, metembonate, stearate, tosylate, 2-hydroxy-3-naphthoate, 3-hydroxy-2-naphthoate or mesylate.
Preferred possible salts for compounds of the present invention are pharmacologically tolerated basic salts, in particular, pharmacologically tolerated salts with the inorganic and organic bases usually used in galenics. Examples of basic salts which may be mentioned are the lithium, sodium, potassium, calcium, aluminium, magnesium, titanium, ammonium or guanidinium salts.
Among the Helicobacter strains against which the compounds of the present invention have proved to be active, the Helicobacter pylori strain may be mentioned in particular as being preferred.
Examples which may be mentioned of medicaments to be administered orally are tablets, coated tablets, hard and soft capsules, for example of gelatine, dispersible powders, granules, aqueous and oily suspensions, emulsions, solutions or syrups, it being advantageous for the tablets, coated tablets, capsules or granules to be such that they readily dissolve in gastric juice and release the active compound in the stomach.
For combined treatment of gastric diseases which are based both on an increased secretion of gastric acid and on damage to the stomach by Helicobacter pylori, there may also be mentioned those drug formulations to be administered orally which contain active compounds of the present invention both in a form which is resistant to gastric juice and in a form which is not resistant to gastric juice simultaneously in an individual dose. Examples which may be mentioned are tablets which contain the active compound both - 4 - 99471/3 in a core which is resistant to gastric juice and in a shell which is not resistant to gastric juice, or capsules filled with pellets or (mini) tablets which are resistant to gastric juice and those which are not reistant to gastric juice.
In human medicine, the active compounds are in general administered in a daily dose of about 0.05 to about 5, preferably 0.,1 to 2.5 mg/kg of body weight, if available . in the form of several, preferably 2 to 6, individual doses to achieve the desired result.
If the compounds of the present invention and/or their salts are to be employed for the treatment of diseases of the stomach, based on the presence of Helicobacter pylori, the medicaments to be administered can also contain one or more pharmacologically active constituents of other groups of medicaments.
Combination of the compounds of the present invention and/or their salts with antimicrobial substances which have an action against Helicobacter pylori, such as, for example, penicillin G, gentamycin, erythromycin, nitrofurazone, nitrofurantoin, furazolidone, metronidazole, and in particular amoxycillin, with the aim of intensifying the main action in the super-additive sense, is to be emphasized in particular in this "ooiinectionT Combination of the active compound 5-difluoromethoxy-2-[ ( 3 , 4-dimethoxy-2-pyridyl) -methylsulphinyl] -lH-benzimidazole [= pantoprazole (INN)] and its salts with substances having an antimicrobial action, in particular with amoxycillin, is particularly preferred in this connection, and the invention therefore furthermore relates to this combination. - 5 - 99471/3 It has been found, surprisingly, that the compounds of the present invention are considerably more active against Helicobacter bacteria in an acid medium than in a neutral medium, and that they accordingly - in contrast to the doctrine found in the prior art - should appropriately not be administered in a form which is resistant to gastric juice.
The invention thus preferably relates to the use of the compounds described herein and their pharmacologically tolerated salts for the preparation of medicaments which are not in a formulation which is resistant to gastric juice, and which are to be administered orally for combatting Helicobacter bacteria.
The medicaments to be administered orally are prepared using the active compounds of the present invention in a manner which is known per se to the expert.
Claims (3)
1. A pharmaceutical composition to be administered orally for combatting Helicobacter bacteria, containing 5-difluoro-methoxy-2- [ ( 3 , 4-dimethoxy-2-pYridyl)methylsulphinyl3 -1H-benzimidazole and/or its pharmacologically tolerated salt, in combination with an antimicrobial agent chosen from the group comprising penicillin G, gentamycin, erythromycin, nitrofurazone, nitrofurantoin, furazolidone, metronidazole and amoxycillin.
2. A pharmaceutical composition to be administered orally for combatting Heliobacter pylori, containing 5-difluoro-methoxy-2-[ ( 3 , 4-dimethoxy-2-pyridyl)methylsulphinyl] -1H-benzimidazole , in combination with amoxycillin.
3. A process for the preparation of pharmaceutical preparations which contain one or more compounds according to claim 1 or 2 as the active compound and customary excipients, characterized in that the active compound which has been prepared in a known manner is mixed with the customary excipients and the mixture is converted into a medicament to be administered orally for combatting Heliobacter bacteria. for the Applicant: WOLFF, BREGMA AND GOLLER
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH299390 | 1990-09-14 | ||
| CH222691 | 1991-07-25 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL99471A0 IL99471A0 (en) | 1992-08-18 |
| IL99471A true IL99471A (en) | 1996-03-31 |
Family
ID=25689847
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9947191A IL99471A (en) | 1990-09-14 | 1991-09-12 | Pharmaceutical compositions for treating helicobacter bacteria infections containing 5-fluoromethoxy-2-(3,4-dimethoxy-2-pyridyl)methylsulphinyl)-1h-benzimidazole and salts thereof in combination with an antimicrobial agent |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP0548103B1 (en) |
| JP (1) | JPH06500547A (en) |
| AT (1) | ATE209914T1 (en) |
| AU (1) | AU8445791A (en) |
| CA (1) | CA2092694C (en) |
| CY (1) | CY2363B1 (en) |
| DE (1) | DE59109225D1 (en) |
| DK (1) | DK0548103T3 (en) |
| ES (1) | ES2169022T3 (en) |
| IE (1) | IE913232A1 (en) |
| IL (1) | IL99471A (en) |
| NZ (1) | NZ239772A (en) |
| WO (1) | WO1992004898A1 (en) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IS3990A (en) * | 1992-04-24 | 1993-10-25 | Ab Astra | Method of mixing substances that inhibit gastric acid and bacterial degrading agent in an acidic environment |
| WO1994019346A1 (en) * | 1993-02-17 | 1994-09-01 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Substituted heteroarylalkylthiopyridines for controlling helicobacter bacteria |
| WO1994027606A1 (en) * | 1993-05-28 | 1994-12-08 | Unisearch Limited | Method of treating helicobacter pylori infection |
| JPH0717971A (en) * | 1993-07-02 | 1995-01-20 | Takeda Chem Ind Ltd | Imidazole derivative, production and use thereof |
| WO1995004045A1 (en) * | 1993-07-28 | 1995-02-09 | Rhone-Poulenc Rorer Limited | Compounds as pde iv and tnf inhibitors |
| ATE192932T1 (en) * | 1993-09-09 | 2000-06-15 | Takeda Chemical Industries Ltd | FORMULATION CONTAINING AN ANTIBACTERIAL AND AN ANTIULCUS ACTIVE |
| US5840737A (en) | 1996-01-04 | 1998-11-24 | The Curators Of The University Of Missouri | Omeprazole solution and method for using same |
| US6489346B1 (en) | 1996-01-04 | 2002-12-03 | The Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and method of using same |
| WO1997040039A1 (en) * | 1996-04-23 | 1997-10-30 | Yoshitomi Pharmaceutical Industries, Ltd. | Pyridine compounds and medicinal uses thereof |
| US8993599B2 (en) | 2003-07-18 | 2015-03-31 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
| US8906940B2 (en) | 2004-05-25 | 2014-12-09 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL85472A (en) * | 1987-03-09 | 1991-06-30 | Procter & Gamble | Pharmaceutical compositions for treating gastrointestinal disorders |
| JPH03504497A (en) * | 1988-05-25 | 1991-10-03 | ビイク グルデン ロンベルク ヒエーミツシエ フアブリーク ゲゼルシヤフト ミツト ベシユレンクテル ハフツング | New fluoroalkoxy compound |
| JP2694361B2 (en) * | 1989-02-09 | 1997-12-24 | アストラ アクチエボラグ | Antibacterial agent |
| ES2066120T3 (en) * | 1989-02-10 | 1995-03-01 | Takeda Chemical Industries Ltd | USE OF BENCIMIDAZOLE DERIVATIVES AS ANTIBACTERIAL AGENTS. |
-
1991
- 1991-09-06 ES ES91914905T patent/ES2169022T3/en not_active Expired - Lifetime
- 1991-09-06 AU AU84457/91A patent/AU8445791A/en not_active Abandoned
- 1991-09-06 DK DK91914905T patent/DK0548103T3/en not_active Application Discontinuation
- 1991-09-06 CA CA002092694A patent/CA2092694C/en not_active Expired - Lifetime
- 1991-09-06 AT AT91914905T patent/ATE209914T1/en not_active IP Right Cessation
- 1991-09-06 WO PCT/EP1991/001689 patent/WO1992004898A1/en not_active Ceased
- 1991-09-06 EP EP91914905A patent/EP0548103B1/en not_active Expired - Lifetime
- 1991-09-06 DE DE59109225T patent/DE59109225D1/en not_active Expired - Lifetime
- 1991-09-06 JP JP3514343A patent/JPH06500547A/en active Pending
- 1991-09-12 IL IL9947191A patent/IL99471A/en not_active IP Right Cessation
- 1991-09-12 NZ NZ239772A patent/NZ239772A/en not_active IP Right Cessation
- 1991-09-13 IE IE323291A patent/IE913232A1/en not_active IP Right Cessation
-
2003
- 2003-05-30 CY CY0300045A patent/CY2363B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES2169022T3 (en) | 2002-07-01 |
| DK0548103T3 (en) | 2002-04-02 |
| EP0548103A1 (en) | 1993-06-30 |
| WO1992004898A1 (en) | 1992-04-02 |
| AU8445791A (en) | 1992-04-15 |
| IL99471A0 (en) | 1992-08-18 |
| EP0548103B1 (en) | 2001-12-05 |
| DE59109225D1 (en) | 2002-01-17 |
| IE913232A1 (en) | 1992-02-25 |
| CA2092694A1 (en) | 1992-03-15 |
| ATE209914T1 (en) | 2001-12-15 |
| CY2363B1 (en) | 2004-06-04 |
| JPH06500547A (en) | 1994-01-20 |
| CA2092694C (en) | 2005-04-05 |
| NZ239772A (en) | 1997-03-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| EXP | Patent expired |