WO1997002039A1 - Antibacterial synergistic composition comprising rifabutin - Google Patents
Antibacterial synergistic composition comprising rifabutin Download PDFInfo
- Publication number
- WO1997002039A1 WO1997002039A1 PCT/EP1996/002493 EP9602493W WO9702039A1 WO 1997002039 A1 WO1997002039 A1 WO 1997002039A1 EP 9602493 W EP9602493 W EP 9602493W WO 9702039 A1 WO9702039 A1 WO 9702039A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- rifabutin
- bismuth
- helicobacter pylori
- proton pump
- treatment
- Prior art date
Links
- ZWBTYMGEBZUQTK-PVLSIAFMSA-N [(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,32-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-1'-(2-methylpropyl)-6,23-dioxospiro[8,33-dioxa-24,27,29-triazapentacyclo[23.6.1.14,7.05,31.026,30]tritriaconta-1(32),2,4,9,19,21,24,26,30-nonaene-28,4'-piperidine]-13-yl] acetate Chemical compound CO[C@H]1\C=C\O[C@@]2(C)Oc3c(C2=O)c2c4NC5(CCN(CC(C)C)CC5)N=c4c(=NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)c(O)c2c(O)c3C ZWBTYMGEBZUQTK-PVLSIAFMSA-N 0.000 title claims abstract description 32
- 229960000885 rifabutin Drugs 0.000 title claims abstract description 32
- 239000000203 mixture Substances 0.000 title claims abstract description 10
- 230000002195 synergetic effect Effects 0.000 title claims abstract description 10
- 230000000844 anti-bacterial effect Effects 0.000 title abstract description 9
- 241000590002 Helicobacter pylori Species 0.000 claims abstract description 20
- 229940037467 helicobacter pylori Drugs 0.000 claims abstract description 20
- 238000002360 preparation method Methods 0.000 claims abstract description 20
- 229910052797 bismuth Inorganic materials 0.000 claims abstract description 19
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229940126409 proton pump inhibitor Drugs 0.000 claims abstract description 17
- 239000000612 proton pump inhibitor Substances 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims description 15
- 230000000694 effects Effects 0.000 claims description 14
- 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 claims description 11
- 229960000381 omeprazole Drugs 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 206010019375 Helicobacter infections Diseases 0.000 claims description 5
- 229960004645 bismuth subcitrate Drugs 0.000 claims description 5
- ZQUAVILLCXTKTF-UHFFFAOYSA-H bismuth;tripotassium;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [K+].[K+].[K+].[Bi+3].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O ZQUAVILLCXTKTF-UHFFFAOYSA-H 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 208000007882 Gastritis Diseases 0.000 claims description 3
- 208000008469 Peptic Ulcer Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- PSIREIZGKQBEEO-UHFFFAOYSA-N 2-(1h-benzimidazol-2-ylsulfinylmethyl)-n-methyl-n-(2-methylpropyl)aniline Chemical compound CC(C)CN(C)C1=CC=CC=C1CS(=O)C1=NC2=CC=CC=C2N1 PSIREIZGKQBEEO-UHFFFAOYSA-N 0.000 claims 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 claims description 2
- 229960003174 lansoprazole Drugs 0.000 claims description 2
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 claims description 2
- 229950007395 leminoprazole Drugs 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 229960005019 pantoprazole Drugs 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- -1 N-isobutyl-4-piperidyl Chemical group 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- ZYECOAILUNWEAL-NUDFZHEQSA-N (4z)-4-[[2-methoxy-5-(phenylcarbamoyl)phenyl]hydrazinylidene]-n-(3-nitrophenyl)-3-oxonaphthalene-2-carboxamide Chemical compound COC1=CC=C(C(=O)NC=2C=CC=CC=2)C=C1N\N=C(C1=CC=CC=C1C=1)/C(=O)C=1C(=O)NC1=CC=CC([N+]([O-])=O)=C1 ZYECOAILUNWEAL-NUDFZHEQSA-N 0.000 description 1
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- HJLSLZFTEKNLFI-UHFFFAOYSA-N Tinidazole Chemical compound CCS(=O)(=O)CCN1C(C)=NC=C1[N+]([O-])=O HJLSLZFTEKNLFI-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000012153 long-term therapy Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229960000282 metronidazole Drugs 0.000 description 1
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229960005053 tinidazole Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/245—Bismuth; Compounds 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to anti-bacterial pharmaceutical compositions against Helicobacter pylori and to their preparation.
- Helicobacter pylori plays a main role in the pathogenesis of gastritis and peptic ulcer.
- Known treatments include the use of amoxicilin or other antibacterial agents in dual or triple combination with other drugs, such as bismuth preparation ⁇ , metronidazole, tinidazole or with proton pump inhibitors, e.g. omeprazole.
- Such combinations have a relatively short duration of action and require high doses and repeated administrations (3-4 times per day) owing to the pharmacokinetics or the low antibacterial activity of the antibiotic and its limited stability in the stomach.
- the present invention provides a pharmaceutical composition suitable for use in the treatment of a
- Helicobacter pylori infection which compo ⁇ ition comprise ⁇ :
- Rifabutin has the structural formula
- Rifabutin is a red violet powder soluble in chloroform and methanol, and very slighly soluble in water; it has a melting point of 148°C-156° (with decomposition) .
- a proton pump inhibitor is typically omeprazole, lansoprazole, leminoprazole, pantoprazole or robeprazole; a bismuth preparation is typically bismuth subsalicyclate or bismuth subcitrate sol (dried) .
- the pharmaceutical composition of the invention may further comprise a pharmaceutically acceptable carrier or diluent.
- the pharmaceutical composition according to the present invention shows an excellent antibacterial activity, good oral bioavailability and stability at low pH, and it is therefore suited for the treatment of Helicobater pylori infections. It was found that the activity of the composition of the invention is greater than the sum of the individual components. A noticeable antibacterial synergistic effect is evident.
- a pharmaceutical composition according to the invention possesses a good activity against Helicobacter pylori at small doses, which are insufficient when the components are used individually. Consequently, the combination of the two components according to the invention is more effective in the treatment of diseases caused by Helicobacter pylori , because it possesses a better therapeutic value than the individual antibiotic.
- antibacterials should not be used as monotheraphy to avoid the emergence of resistant strains. This is particularly important for long term therapy.
- the invention further provides a process for preparing the above mentioned composition, which process comprises mixing:
- (III) optionally, a pharmaceutically acceptable carrier or diluent .
- Suitable carriers or diluents are those conventionally used in pharmaceutical preparations .
- the carrier or diluent commonly comprises starches and binders and/or lubricants.
- the present invention also provides a pharmaceutical composition a ⁇ defined above for use in the treatment of a disease caused by Helicobacter pylori.
- the two components may be mixed immediately prior to administration. Then they be presented in a form suitable for combined administration in the treatment of disorders caused by Helicobacter pylori .
- the present invention therefore also provides products comprising: (I) rifabutin; and
- the daily doses of individual components in compositions according to the invention are lower as compared to the active doses of the individual components, when used without the other component.
- the weight ratio of rifabutin to proton pump inhibitor or bismuth preparation is generally from 1:100 to 100:1. Where the composition of the invention comprises rifabutin and a proton pump inhibitor, the weight ratio of rifabutin:proton pump inhibitor is typically from 25:1 to 5:1. Where the composition comprises rifabutin and a bismuth preparation, the weight ratio of rifabutin:bismuth preparation is typically from 1:10 to 10:1. Typically, for adults (70 kg) the daily dose ⁇ of rifabutin ranges from 100 to 1000 mg, preferably from 200 to 500 mg, more preferably 300 mg.
- the daily dose of the proton pump inhibitor is from 1 mg to 1000 mg, preferably from 10 to 100 mg and the daily dose for the bismuth preparation is from 50 mg to 5000 mg, preferably from about 50 mg to about 1000 mg.
- rifabutin and a proton pump inhibitor or bismuth preparation may be used in the treatment of gastrointenstinal disorders in a living being particularly a human.
- the first example concerns the activity of rifabutin and BSM
- the second one concerns the activity of rifabutin and omeprazole.
- the inhibiting drug concentrations are lower when drugs are combined together.
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Pharmaceutical anti-bacterial synergistic compositions against Helicobacter pylori, containing rifabutin and a proton pump inhibitor or a bismuth preparation.
Description
ANTIBACTERIAL SYNERGISTIC COMPOSITION COMPRISING RIFABUTIN
The present invention relates to anti-bacterial pharmaceutical compositions against Helicobacter pylori and to their preparation.
Helicobacter pylori plays a main role in the pathogenesis of gastritis and peptic ulcer.
Known treatments include the use of amoxicilin or other antibacterial agents in dual or triple combination with other drugs, such as bismuth preparationε, metronidazole, tinidazole or with proton pump inhibitors, e.g. omeprazole.
Such combinations have a relatively short duration of action and require high doses and repeated administrations (3-4 times per day) owing to the pharmacokinetics or the low antibacterial activity of the antibiotic and its limited stability in the stomach.
We have discovered that a very effective treatment can be achieved by administration of a synergistic composition. The present invention provides a pharmaceutical composition suitable for use in the treatment of a
Helicobacter pylori infection, which compoεition compriseε:
(I) rifabutin; and
(II) a proton pump inhibitor or a bismuth preparation in a quantity producing a synergistic activity against
Helicobacter pylori .
Rifabu in is the generic name of a chemical compound 4- deoxo-3,4- [2-spiro(N-isobutyl-4-piperidyl) -2,5-dihydro-lH- imidazo] -rifamycin S. Depending on the system used to name a chemical compound, it may also be identified as 6,9-dihydro- 5,17, 19,21-tetrahydroxy-8,9- [2-spiro- (N-isobutyl-4- piperidyl) -2,5 -dihydro-IH-imidazo] -23-methoxy - 2,4, 12, 16,18,20,22-heptamethyl-6-oxo-2, 7- (epoxypentadeca-
[1,11,13] -trienimino) naphthol [2, 1] -b furan-1,11- (2H) -dione- 21-acetate; or (9S,12E, 14S,15R,16S, 17R, 18R, 19R,20S, 21S, 22E,24Z) -6, 16,18,20-tetrahydroxy-l' -isobutyl-14-methyloxy- 7,9,15,17,19,21,25-heptamethyl-spiro[9,4-
(epoxypentadeca[1,11,13] trienimino-2H- furo[2' ,3' ,7,8]naphth[l,2-d] imidazole-2,4' -piperidine-
5,10,26, (3H,9H) -trione-16-acetate.
Rifabutin has the structural formula
Molecular formula : C46HS2N4011 Molecular Weight : 847 . 12
The preparation of rifabutin is described in U.S. Patent 4,219,478 issued on August 26, 1980. Rifabutin is a red violet powder soluble in chloroform and methanol, and very slighly soluble in water; it has a melting point of 148°C-156° (with decomposition) .
A proton pump inhibitor is typically omeprazole, lansoprazole, leminoprazole, pantoprazole or robeprazole; a bismuth preparation is typically bismuth subsalicyclate or bismuth subcitrate sol (dried) . The pharmaceutical composition of the invention may further comprise a pharmaceutically acceptable carrier or diluent.
The pharmaceutical composition according to the present invention shows an excellent antibacterial activity, good oral bioavailability and stability at low pH, and it is therefore suited for the treatment of Helicobater pylori infections. It was found that the activity of the composition of the invention is greater than the sum of the individual components. A noticeable antibacterial synergistic effect is evident.
A pharmaceutical composition according to the invention possesses a good activity against Helicobacter pylori at small doses, which are insufficient when the components are used individually. Consequently, the combination of the two components according to the invention is more effective in the treatment of diseases caused by Helicobacter pylori , because it possesses a better therapeutic value than the individual antibiotic.
In addition, antibacterials should not be used as monotheraphy to avoid the emergence of resistant strains. This is particularly important for long term therapy.
The invention further provides a process for preparing the above mentioned composition, which process comprises mixing:
(I) rifabutin;
(II) a proton pump inhibitor or a bismuth preparation in a quantity producing a synergistic activity against Heli coba cter pyl ori • and
(III) optionally, a pharmaceutically acceptable carrier or diluent .
Suitable carriers or diluents are those conventionally used in pharmaceutical preparations . For example for tablets or capsules the carrier or diluent commonly comprises starches and binders and/or lubricants.
The present invention also provides a pharmaceutical composition aε defined above for use in the treatment of a disease caused by Helicobacter pylori. The two components may be mixed immediately prior to administration. Then they be presented in a form suitable for combined administration in the treatment of disorders caused by Helicobacter pylori . The present invention therefore also provides products comprising: (I) rifabutin; and
(II) a proton pump inhibitor or a bismuth preparation in a quantity producing a synergistic activity against Helicobacter pylori ;
as a combined preparation for simultaneous, separate or sequential use in the treatment of a HelicoJbacter pylori infection.
The daily doses of individual components in compositions according to the invention are lower as compared to the active doses of the individual components, when used without the other component. The weight ratio of rifabutin to proton pump inhibitor or bismuth preparation is generally from 1:100 to 100:1. Where the composition of the invention comprises rifabutin and a proton pump inhibitor, the weight ratio of rifabutin:proton pump inhibitor is typically from 25:1 to 5:1. Where the composition comprises rifabutin and a bismuth preparation, the weight ratio of rifabutin:bismuth preparation is typically from 1:10 to 10:1. Typically, for adults (70 kg) the daily doseε of rifabutin ranges from 100 to 1000 mg, preferably from 200 to 500 mg, more preferably 300 mg.
The daily dose of the proton pump inhibitor is from 1 mg to 1000 mg, preferably from 10 to 100 mg and the daily dose for the bismuth preparation is from 50 mg to 5000 mg, preferably from about 50 mg to about 1000 mg.
The combination of rifabutin and a proton pump inhibitor or bismuth preparation may be used in the treatment of gastrointenstinal disorders in a living being particularly a human.
In vitro bactericidal activity
Tests were carried out on several strains of Helicobacter pylori according to CZI N S. et al . Antimicrobial Agentε Chemoter 3J, 328-329, 1986 and Clinical
Microbiology Procedure Handbook, Isenberg H.D. ed. ASM 1992
(modified) .
In the following tables is reported the activity of rifabutin, omeprazole and bismuth subcitrate sol (BSM) as single drug and in combination, on selected H. pylori strains.
The first example concerns the activity of rifabutin and BSM
, the second one concerns the activity of rifabutin and omeprazole.
As shown in the tables, the inhibiting drug concentrations are lower when drugs are combined together.
Example 1
Combination of rifabutin and bismuth subcitrate sol.
Helibacter pylori strain 46. rifabutin (μg/ml) BSM (μg/ml) effect
0.0037 _ MIC*
— 4 MIC
0.0009 0.5 SYN*
0.00045 1 SYN
Heli cobacter pylori strain 34 rifabutin (μg/ml) BSM (μg/ml) effect
0.0075 — MIC
— 4 MIC
0.0018 0.5 SYN
0.0009 1 SYN
Helicobacter pylori strain 13 rifabutin (μg/ml) BSM (μg/ml) effect
0.0075 — MIC
2 MIC
"
0.0018 0.5 SYN
* MIC: minimal inhibitory concentration ** SYN: inhibited at subMIC concentrations Example 2
Combination of rifabutin and omeprazole Helicobacter pylori strain 35 rifabutin (μg/ml) omeprazole (μg/ml) effect
0.0037 — MIC
— 64 MIC
0.0009 4 SYN
0.00045 16 SYN
0.00022 16 SYN
Helicobacter pylori strain 50 rifabutin (μg/ml) omeprazole (μg/ml) effect
0.0075 — MIC
~" 32 MIC
0.0018 4 SYN
0.0018 2 SYN rifabutin (μg/ml) omeprazole (μg/ml) effect
0.0009 8 SYN
Helicobacter pylori strain 43
rifabutin (μg/ml) omeprazole (μg/ml) effect
0.0075 ~ MIC
— 64 MIC
0.0018 2 SYN
0.0009 8 SYN
0.00045 16 SYN
0.00022 16 SYN
Claims
1. A pharmaceutical composition suitable for use in the treatment of a Helicobacter pylori infection, which composition comprises: (I) rifabutin; and
(II) a proton pump inhibitor or a bismuth preparation in a quantity producing a synergistic activity against Heli coba cter pyl ori .
2. A pharmaceutical composition according to claim 1 further comprising a pharmaceutically acceptable carrier or diluent .
3. A pharmaceutical compoεition according to claim 1 or 2 , wherein the proton pump inhibitor is selected from omeprazole, lansoprazole, leminoprazole, pantoprazole or robeprazole; or the bismuth preparation is selected from bismuth subsalicyclate or bismuth subcitrate sol (dried) .
4. A pharmaceutical composition according to claim 3 wherein the proton pump inhibitor iε omeprazole or the bismuth preparation is bismuth subcitrate sol (dried) .
5. A process for preparing a pharmaceutical compoεition according to any one of claimε 1 to 4, which proceεε compriεeε mixing:
(I) rifabutin;
(II) a proton pump inhibitor or a bismuth preparation in a quantity producing a synergiεtic activity against Helicobacter pylori ; and
(III) optionally, a pharmaceutically acceptable carrier or diluent.
6. A pharmaceutical composition as defined in any one of claims 1 to 4 for use in the treatment of a Helicobacter pylori infection.
7. A pharmaceutical composition according to claim 6 for use in the treatment of gastritis or peptic ulcers.
8. Use, in the manufacture of a medicament for use in the treatment of a Helicobacter pylori infection, of:
(I) rifabutin; and (II) a proton pump inhibitor or a bismuth preparation; component (II) being present in an amount producing a synergiεtic activity againεt Helicobacter pylori .
9. The uεe according to claim 8 wherein the medicament iε for use in the treatment of gastritis or peptic ulcers.
10. Products containing:
(I) rifabutin; and
(II) a proton pump inhibitor or a bismuth preparation in a quantity producing a synergistic activity against
Heli coba cter pyl ori ; aε a combined preparation for simultaneouε, separate or sequential use in the treatment of a Helicobacter pylori infection.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP96921953A EP0836477A1 (en) | 1995-07-04 | 1996-06-07 | Antibacterial synergistic composition comprising rifabutin |
| JP9504744A JPH11508566A (en) | 1995-07-04 | 1996-06-07 | Antibacterial synergistic composition containing rifabutin |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9513551.3 | 1995-07-04 | ||
| GBGB9513551.3A GB9513551D0 (en) | 1995-07-04 | 1995-07-04 | Anti-bacterial synergistic composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1997002039A1 true WO1997002039A1 (en) | 1997-01-23 |
Family
ID=10777071
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1996/002493 WO1997002039A1 (en) | 1995-07-04 | 1996-06-07 | Antibacterial synergistic composition comprising rifabutin |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0836477A1 (en) |
| JP (1) | JPH11508566A (en) |
| GB (1) | GB9513551D0 (en) |
| WO (1) | WO1997002039A1 (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0861660A1 (en) * | 1997-02-28 | 1998-09-02 | Kaneka Corporation | Curative medicine for disease caused by infection of Helicobacter |
| US5981522A (en) * | 1995-09-01 | 1999-11-09 | Kaneka Corporation | Treatment of disease caused by infection of Helicobacter |
| WO1999056749A1 (en) * | 1998-04-30 | 1999-11-11 | Borody Thomas J | IMPROVED METHOD FOR ERADICATION OF $i(HELICOBACTER PYLORI) |
| WO2001035899A3 (en) * | 1999-11-19 | 2001-12-13 | Axxima Pharmaceuticals Ag | Inhibitors of helicobacter pylori induced gastrointestinal diseases |
| US6362169B1 (en) | 1998-02-24 | 2002-03-26 | Kaneka Corporation | Antibacterial compositions with synergistic effect, drugs and remedies for digestive diseases containing the same, process for the production thereof and preparations associated therewith |
| AU762890B2 (en) * | 1998-04-30 | 2003-07-10 | Red Hill Biopharma Ltd. | Improved method for eradication of Helicobacter Pylori |
| US6849409B2 (en) | 2000-10-16 | 2005-02-01 | Axxima Pharmaceuticals Ag | Cellular kinases involved in Cytomegalovirus infection and their inhibition |
| RU2320337C1 (en) * | 2006-06-09 | 2008-03-27 | Федеральное государственное унитарное предприятие "Государственный научный центр по антибиотикам" | Method for preparing rifabutin-containing antibacterial composition |
| RU2327457C1 (en) * | 2007-06-26 | 2008-06-27 | Автономная некоммерческая организация "Институт молекулярной диагностики" (АНО "ИнМоДи") | Medicinal agent based on rybafutin, agent of antimicrobic action containing nanoparticles, and related method of production |
-
1995
- 1995-07-04 GB GBGB9513551.3A patent/GB9513551D0/en active Pending
-
1996
- 1996-06-07 EP EP96921953A patent/EP0836477A1/en not_active Withdrawn
- 1996-06-07 JP JP9504744A patent/JPH11508566A/en active Pending
- 1996-06-07 WO PCT/EP1996/002493 patent/WO1997002039A1/en not_active Application Discontinuation
Non-Patent Citations (3)
| Title |
|---|
| J.HOLTON ET AL.: "the susceptibility of helicobacter pylori to the rifamycin rifaximin", J. ANTIMICROB. CHEMOTHER., vol. 35, no. 4, April 1995 (1995-04-01), ENGLAND, pages 545 - 549, XP000600927 * |
| KUNIN, C. M.: "antimicrobial activity of rifabutin", CLIN. INFECTIOUS DISEASES, vol. 22, no. suppl. 1, 1996, UNIVERSITY OF CHICAGO, pages s3 - s14, XP000600925 * |
| M. MENEGATTI ET AL.: "rifaximin suspension for the eradication of helicobacter pylori", AM. JOURNAL OF GASTROENTEROL., vol. 89, no. 8, 1994, 1ST MED. CLIN. UNIV. BOLOGNA ITL, pages 1382, XP000603245 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5981522A (en) * | 1995-09-01 | 1999-11-09 | Kaneka Corporation | Treatment of disease caused by infection of Helicobacter |
| EP0861660A1 (en) * | 1997-02-28 | 1998-09-02 | Kaneka Corporation | Curative medicine for disease caused by infection of Helicobacter |
| US6362169B1 (en) | 1998-02-24 | 2002-03-26 | Kaneka Corporation | Antibacterial compositions with synergistic effect, drugs and remedies for digestive diseases containing the same, process for the production thereof and preparations associated therewith |
| EP1057487A4 (en) * | 1998-02-24 | 2006-09-20 | Activbiotics Inc | Antimicrobial compositions with synergistic effect, drugs and remedies for digestive diseases containing the same, process for the production thereof and preparations associated therewith |
| WO1999056749A1 (en) * | 1998-04-30 | 1999-11-11 | Borody Thomas J | IMPROVED METHOD FOR ERADICATION OF $i(HELICOBACTER PYLORI) |
| US6489317B1 (en) | 1998-04-30 | 2002-12-03 | Thomas Julius Borody | Method for eradication of Helicobacter pylori |
| AU762890B2 (en) * | 1998-04-30 | 2003-07-10 | Red Hill Biopharma Ltd. | Improved method for eradication of Helicobacter Pylori |
| WO2001035899A3 (en) * | 1999-11-19 | 2001-12-13 | Axxima Pharmaceuticals Ag | Inhibitors of helicobacter pylori induced gastrointestinal diseases |
| US6849409B2 (en) | 2000-10-16 | 2005-02-01 | Axxima Pharmaceuticals Ag | Cellular kinases involved in Cytomegalovirus infection and their inhibition |
| RU2320337C1 (en) * | 2006-06-09 | 2008-03-27 | Федеральное государственное унитарное предприятие "Государственный научный центр по антибиотикам" | Method for preparing rifabutin-containing antibacterial composition |
| RU2327457C1 (en) * | 2007-06-26 | 2008-06-27 | Автономная некоммерческая организация "Институт молекулярной диагностики" (АНО "ИнМоДи") | Medicinal agent based on rybafutin, agent of antimicrobic action containing nanoparticles, and related method of production |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH11508566A (en) | 1999-07-27 |
| GB9513551D0 (en) | 1995-09-06 |
| EP0836477A1 (en) | 1998-04-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69626117T2 (en) | ORAL PHARMACEUTICAL COMPOSITIONS WITH DELAYED RELEASE OF REVERSIBLE PROTON PUMP INHIBITORS | |
| CA1171783A (en) | Combination of rapamycin and picibanil for the treatment of tumors | |
| JP2009263371A (en) | Anti-cancer combination | |
| CA2412795A1 (en) | Improved liposomal camptothecins and uses thereof | |
| JPH0692850A (en) | Remedy for gastrointestinal disturbance | |
| WO1997002039A1 (en) | Antibacterial synergistic composition comprising rifabutin | |
| WO2010071308A1 (en) | Composition for improving radiotherapy for cancer | |
| EP0544760B1 (en) | Pharmaceutical compositions containing 5-difluoromethoxy-2- (3,4-dimethoxy-2-pyridyl) methylsulfinyl] benzimidazole and an anti-helicobacter agent for the treatment of gastrointestinal disorders | |
| US6426369B1 (en) | Oxethazaine as antimicrobial agent | |
| CZ71298A3 (en) | Bismuth salt of antibiotics selected from the group of monomycins, process of their preparation, their use and medicament in which said compounds are comprised | |
| US20060194829A1 (en) | Therapeutic materials and methods | |
| EP0190851B1 (en) | Improved antiinflammatory composition | |
| JPH07242560A (en) | Antimicrobial | |
| JPH072672A (en) | Antibacterial formulation | |
| EP0218453A1 (en) | Improved antiinflammatory compositions and methods | |
| KR100572090B1 (en) | Synergistic antimicrobial compositions, medicaments containing the same and agents for treating digestive diseases, methods for their preparation, and agents related thereto | |
| Vilmgnyi et al. | Clarithromycin pharmacokinetics after oral administration with or without fasting in crossbred beagles | |
| AU740642B2 (en) | Pharmaceutical compositions containing cinchonine dichlorhydrate | |
| Darzentas et al. | Effect of antacid on bioavailability of a sustained-release theophylline preparation | |
| WO2017007120A1 (en) | Pharmaceutical composition for treating renal diseases, containing dipyridamole as active ingredient | |
| Chew et al. | Paromomycin | |
| IE950090A1 (en) | Pharmaceutical composition | |
| JP2000080031A (en) | Antimicrobial agent | |
| EP0384722A1 (en) | Chemical compositions | |
| WO1996019232A1 (en) | Combinations of ranitidine hydrochloride-form 1 and bismuth compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): JP |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| ENP | Entry into the national phase |
Ref country code: JP Ref document number: 1997 504744 Kind code of ref document: A Format of ref document f/p: F |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 1996921953 Country of ref document: EP |
|
| WWP | Wipo information: published in national office |
Ref document number: 1996921953 Country of ref document: EP |
|
| WWW | Wipo information: withdrawn in national office |
Ref document number: 1996921953 Country of ref document: EP |