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WO1996019489A1 - Composes - Google Patents

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Publication number
WO1996019489A1
WO1996019489A1 PCT/IE1995/000065 IE9500065W WO9619489A1 WO 1996019489 A1 WO1996019489 A1 WO 1996019489A1 IE 9500065 W IE9500065 W IE 9500065W WO 9619489 A1 WO9619489 A1 WO 9619489A1
Authority
WO
WIPO (PCT)
Prior art keywords
roxithromycin
clarithromycin
azithromycin
acetylcystein
compound
Prior art date
Application number
PCT/IE1995/000065
Other languages
English (en)
Inventor
Helmut Schickaneder
Aggelos Nikolopoulos
Declan Kelly
Original Assignee
Russinsky Limited
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 Russinsky Limited filed Critical Russinsky Limited
Priority to AU43993/96A priority Critical patent/AU4399396A/en
Publication of WO1996019489A1 publication Critical patent/WO1996019489A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
    • C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals

Definitions

  • the present invention relates to new antibiotic and mucolytic salts of roxithromycin, clarithromycin and azithromcyin.
  • the invention is directed towards providing antibiotic and mucolytic salts.
  • R is a radical selected from :
  • Clarithromycin has the structure
  • Azithromycin has the structure
  • the compounds according to the invention are white microcrystalline powders .
  • compositions will typically contain suitable excipients and/or vehicles which are conventionally used in galenical pharmacy.
  • the method for the preparation of the new salts comprises reacting roxithromycin, clarithromycin or azithromycin base with N-acetylcystein in a stoichiometrical ratio or preferably with a slight excess of the antibiotic nucleus. Most preferably the reaction is carried out in an organic solvent, at a temperature of between 20 and 40°C and in the presence of water, preferably in an amount of not greater than 20%.
  • the reactions may be carried out in a suspension of water at a temperature of 20 and 40°C, (with N-acetylcystein in a stoichiometrical ratio or in the presence of a slight excess of the antibiotic nucleus), and after building the salts, water is distilled off under very mild conditions (low vacuum, low temperature) .
  • test organism was maintained through periodic inoculations on agar slants containing USP 23 Medium No. 1. The slants are incubated at 32-35°C for 24 hours, and stored under refrigeration.
  • Assay plates Sterile plastic petri-dishes (ca. 20 x 100mm) with covers were used as assay plates. Assay cylinders were manufactured from stainless steel (o.d. 8mm ⁇ 0.1mm, i.d. 6mm + 0.1mm, length 10mm ⁇ 0.1mm).
  • Buffer Solution No. 3 fUSP 23. (0.1M potassium phosphate buffer pH 8.0) Dibasic potassium phosphate 16.73g Monobasic potassium phosphate 0.523g Purified Water 1000ml
  • Test Sample (Roxithromycin Stinoprate):
  • Stinoprate test substance was compared to the standard curve obtained for the Erythromycin Stinoprate standard dilutions. This was calculated as a percentage of the potency of the 1.0 ⁇ g/ml Erythromycin Stinoprate standard dilution.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)

Abstract

L'invention porte sur des sels de roxithromycine, de clarithromycine et d'azithromycine, agissant comme antibiotique et fluidifiant. Elle porte notamment sur le stinoprate de roxithromycine qui s'avère plus actif que le stinoprate d'érythromycine.
PCT/IE1995/000065 1994-12-19 1995-12-19 Composes WO1996019489A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU43993/96A AU4399396A (en) 1994-12-19 1995-12-19 Compounds

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IE940973 1994-12-19
IE940973 1994-12-19

Publications (1)

Publication Number Publication Date
WO1996019489A1 true WO1996019489A1 (fr) 1996-06-27

Family

ID=11040597

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IE1995/000065 WO1996019489A1 (fr) 1994-12-19 1995-12-19 Composes

Country Status (2)

Country Link
AU (1) AU4399396A (fr)
WO (1) WO1996019489A1 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998005674A1 (fr) * 1996-08-07 1998-02-12 Russinsky Limited Procede pour la production de sels d'erythromycine, de roxithromycine, de clarithromycine et d'azithromycine
EP0925789A1 (fr) * 1997-12-02 1999-06-30 Pfizer Products Inc. Composition topique contenant de l'azithromycine pour le traitement d'infections oculaires
WO2000023081A1 (fr) * 1998-10-20 2000-04-27 Lauteral Limited Derives d'erythromycine, de clarithromycine, de roxithromycine ou d'azithromycine ayant une activite antibiotique et mucolytique
US6569443B1 (en) 1999-03-31 2003-05-27 Insite Vision, Inc. Topical treatment or prevention of ocular infections
US6861411B1 (en) 1997-12-02 2005-03-01 Pfizer, Inc. Method of treating eye infections with azithromycin
US7056893B2 (en) 1999-03-31 2006-06-06 Insite Vision, Inc. Topical treatment for prevention of ocular infections
EP1446010A4 (fr) * 2001-10-18 2007-06-13 Teva Pharma Compositions d'azithromycine stabilisees
US7468428B2 (en) 2004-03-17 2008-12-23 App Pharmaceuticals, Llc Lyophilized azithromycin formulation
US7723389B2 (en) * 2001-03-30 2010-05-25 The Board Of Trustees Of The Leland Stanford Junior University N-acetylcysteine compositions and methods for the treatment and prevention of drug toxicity

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0057489A1 (fr) * 1981-02-02 1982-08-11 REFARMED, Recherches Pharmaceutiques et Médicales S.A. Dérivés d'érythromycine contenant du soufre ayant une activité thérapeutique, procédé pour leur préparation et compositions pharmaceutiques les contenant
FR2534588A2 (fr) * 1982-10-15 1984-04-20 Roussel Uclaf Nouvelles oximes derivees de l'erythromycine, leur procede de preparation et leur application comme medicaments

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0057489A1 (fr) * 1981-02-02 1982-08-11 REFARMED, Recherches Pharmaceutiques et Médicales S.A. Dérivés d'érythromycine contenant du soufre ayant une activité thérapeutique, procédé pour leur préparation et compositions pharmaceutiques les contenant
FR2534588A2 (fr) * 1982-10-15 1984-04-20 Roussel Uclaf Nouvelles oximes derivees de l'erythromycine, leur procede de preparation et leur application comme medicaments

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
M. DE BERNARDI ET AL.: "Human pharmacokinetics of erythryomycin propionate-N-acetylcysteinate", INT. J. CLIN. PHARMACOL. THER. TOXICOL., vol. 26, 1988, pages 444 - 7, XP002002013 *
M.F. PARRY AND H. NEU: "Effect of N-Acetylcysteine on Antibiotic Activity and Bacterial Growth In Vitro", J. CLIN. MICROBIOL., vol. 5, 1977, pages 58 - 61, XP002002481 *
N. BAHAL AND M.C. NAHATA: "The new macrolide antibiotics: azithromycin, clarithromycin, dirithromycin and roxithromycin", ANNAL. PHARMACOTHER., vol. 26, 1992, pages 46 - 55, XP002002015 *
O. PAULSEN ET AL.: "No effect of oral N-acetylcysteine on the bioavailability of erythromycin and bacampicillin", EUR. J. RESPIR., vol. 1, 1988, pages 171 - 5, XP002002014 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998005674A1 (fr) * 1996-08-07 1998-02-12 Russinsky Limited Procede pour la production de sels d'erythromycine, de roxithromycine, de clarithromycine et d'azithromycine
EP0925789A1 (fr) * 1997-12-02 1999-06-30 Pfizer Products Inc. Composition topique contenant de l'azithromycine pour le traitement d'infections oculaires
US6861411B1 (en) 1997-12-02 2005-03-01 Pfizer, Inc. Method of treating eye infections with azithromycin
AU760884B2 (en) * 1998-10-20 2003-05-22 Russinsky Limited Derivatives of erythromycin, clarithromycin, roxithromycin or azithromycin with antibiotic and mucolytic activity
US6599885B2 (en) 1998-10-20 2003-07-29 Russinsky Limited Derivatives of erythromycin, clarithromycin, roxithromycin or azithromycin with antibiotic and mucolytic activity
WO2000023081A1 (fr) * 1998-10-20 2000-04-27 Lauteral Limited Derives d'erythromycine, de clarithromycine, de roxithromycine ou d'azithromycine ayant une activite antibiotique et mucolytique
US6569443B1 (en) 1999-03-31 2003-05-27 Insite Vision, Inc. Topical treatment or prevention of ocular infections
US7056893B2 (en) 1999-03-31 2006-06-06 Insite Vision, Inc. Topical treatment for prevention of ocular infections
US7732415B2 (en) 1999-03-31 2010-06-08 Insite Vision Incorporated Topical treatment or prevention of ocular infections
US7749970B2 (en) 1999-03-31 2010-07-06 Insite Vision Incorporated Topical treatment of prevention of ocular infections
US7723389B2 (en) * 2001-03-30 2010-05-25 The Board Of Trustees Of The Leland Stanford Junior University N-acetylcysteine compositions and methods for the treatment and prevention of drug toxicity
EP1446010A4 (fr) * 2001-10-18 2007-06-13 Teva Pharma Compositions d'azithromycine stabilisees
US7468428B2 (en) 2004-03-17 2008-12-23 App Pharmaceuticals, Llc Lyophilized azithromycin formulation

Also Published As

Publication number Publication date
AU4399396A (en) 1996-07-10

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