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WO1997002039A1 - Composition synergique antibacterienne a base de rifabutine - Google Patents

Composition synergique antibacterienne a base de rifabutine Download PDF

Info

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
Application number
PCT/EP1996/002493
Other languages
English (en)
Inventor
Rosaria Rossi
Daniela Jabes
Paola Castellani
Original Assignee
Pharmacia & Upjohn S.P.A.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pharmacia & Upjohn S.P.A. filed Critical Pharmacia & Upjohn S.P.A.
Priority to JP9504744A priority Critical patent/JPH11508566A/ja
Priority to EP96921953A priority patent/EP0836477A1/fr
Publication of WO1997002039A1 publication Critical patent/WO1997002039A1/fr

Links

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)
  • Chemical & Material Sciences (AREA)
  • Public Health (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)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

L'invention concerne des compositions synergiques antibactériennes pharmaceutiques agissant contre l'Helicobacter pylori. Ces compositions contiennent de la rifabutine et un inhibiteur de la pompe à protons ou une préparation de bismuth.
PCT/EP1996/002493 1995-07-04 1996-06-07 Composition synergique antibacterienne a base de rifabutine WO1997002039A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP9504744A JPH11508566A (ja) 1995-07-04 1996-06-07 リファブチンを含む抗細菌相乗性組成物
EP96921953A EP0836477A1 (fr) 1995-07-04 1996-06-07 Composition synergique antibacterienne a base de rifabutine

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9513551.3A GB9513551D0 (en) 1995-07-04 1995-07-04 Anti-bacterial synergistic composition
GB9513551.3 1995-07-04

Publications (1)

Publication Number Publication Date
WO1997002039A1 true WO1997002039A1 (fr) 1997-01-23

Family

ID=10777071

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1996/002493 WO1997002039A1 (fr) 1995-07-04 1996-06-07 Composition synergique antibacterienne a base de rifabutine

Country Status (4)

Country Link
EP (1) EP0836477A1 (fr)
JP (1) JPH11508566A (fr)
GB (1) GB9513551D0 (fr)
WO (1) WO1997002039A1 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0861660A1 (fr) * 1997-02-28 1998-09-02 Kaneka Corporation Médicament pour trouble induit par l'hélicobacter
US5981522A (en) * 1995-09-01 1999-11-09 Kaneka Corporation Treatment of disease caused by infection of Helicobacter
WO1999056749A1 (fr) * 1998-04-30 1999-11-11 Borody Thomas J Methode amelioree d'eradication d'helicobacter pylori
WO2001035899A3 (fr) * 1999-11-19 2001-12-13 Axxima Pharmaceuticals Ag Inhibiteurs de maladies gastro-intestinales induites par helicobacter pilori
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 (ru) * 2006-06-09 2008-03-27 Федеральное государственное унитарное предприятие "Государственный научный центр по антибиотикам" Способ получения антимикробной композиции с рифабутином
RU2327457C1 (ru) * 2007-06-26 2008-06-27 Автономная некоммерческая организация "Институт молекулярной диагностики" (АНО "ИнМоДи") Лекарственное средство на основе рифабутина, препарат противомикробного действия, содержащий наночастицы, и способ его получения

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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 (fr) * 1997-02-28 1998-09-02 Kaneka Corporation Médicament pour trouble induit par l'hélicobacter
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 (fr) * 1998-02-24 2006-09-20 Activbiotics Inc Compositions antimicrobiennes a effet synergique, medicaments et remedes pour maladies digestives contenant ces compositions, leur procede de production et preparations associees
WO1999056749A1 (fr) * 1998-04-30 1999-11-11 Borody Thomas J Methode amelioree d'eradication d'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 (fr) * 1999-11-19 2001-12-13 Axxima Pharmaceuticals Ag Inhibiteurs de maladies gastro-intestinales induites par helicobacter pilori
US6849409B2 (en) 2000-10-16 2005-02-01 Axxima Pharmaceuticals Ag Cellular kinases involved in Cytomegalovirus infection and their inhibition
RU2320337C1 (ru) * 2006-06-09 2008-03-27 Федеральное государственное унитарное предприятие "Государственный научный центр по антибиотикам" Способ получения антимикробной композиции с рифабутином
RU2327457C1 (ru) * 2007-06-26 2008-06-27 Автономная некоммерческая организация "Институт молекулярной диагностики" (АНО "ИнМоДи") Лекарственное средство на основе рифабутина, препарат противомикробного действия, содержащий наночастицы, и способ его получения

Also Published As

Publication number Publication date
GB9513551D0 (en) 1995-09-06
JPH11508566A (ja) 1999-07-27
EP0836477A1 (fr) 1998-04-22

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