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WO1996037191A1 - Compositions antibacteriennes - Google Patents

Compositions antibacteriennes Download PDF

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Publication number
WO1996037191A1
WO1996037191A1 PCT/US1995/006587 US9506587W WO9637191A1 WO 1996037191 A1 WO1996037191 A1 WO 1996037191A1 US 9506587 W US9506587 W US 9506587W WO 9637191 A1 WO9637191 A1 WO 9637191A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
ciprofloxacin
polystyrene sulfonic
concentration
compositions
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US1995/006587
Other languages
English (en)
Inventor
Yusuf Ali
Rajni Jani
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alcon Vision LLC
Original Assignee
Alcon Laboratories Inc
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 Alcon Laboratories Inc filed Critical Alcon Laboratories Inc
Priority to PCT/US1995/006587 priority Critical patent/WO1996037191A1/fr
Priority to JP52719495A priority patent/JP2944759B2/ja
Priority to AU27621/95A priority patent/AU705718B2/en
Publication of WO1996037191A1 publication Critical patent/WO1996037191A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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
    • A61K31/74—Synthetic polymeric materials
    • A61K31/795—Polymers containing sulfur
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
    • A61K47/585—Ion exchange resins, e.g. polystyrene sulfonic acid resin

Definitions

  • the present invention relates to pharmaceutical compositions comprising a synergistic combination of a quinolone, specifically ciprofloxacin, and a polystyrene sulfonic acid polymer.
  • Ciprofloxacin (CiloxanTM, Alcon Laboratories, Inc., Fort Worth, Texas, U.S.A.) is being used to treat ocular bacterial infections.
  • Ciprofloxacin because of the poor solubility of ciprofloxacin at physiological or higher pH, ciprofloxacin formulations were developed at acidic pHs. When these formulations are administered topically to the eye, they can be uncomfortable for some individuals.
  • the present invention is directed to improved topical ophthalmic or otic compositions containing ciprofloxacin and a polystyrene sulfonic acid polymer.
  • the compositions are formulated such that the solubility of ciprofloxacin at a higher pH is increased by the use of an ionic polymer (namely, polystyrene sulfonic acid polymer) which binds with the ciprofloxacin.
  • the binding between the polymer and the ciprofloxacin additionally provides for both initial and continual comfort upon instillation in the eye, as there is less free drug to irritate the tissues of the eye.
  • Another added benefit to the compositions of the present invention is that there is sustained release of the ciprofloxacin.
  • compositions of the present invention contain a synergistic combination of ciprofloxacin having antibacterial activity and a polystyrene sulfonic acid polymer, preferably at physiological or near- physiological pH. These compositions are especially useful in the eye, as the compositions are comfortable upon topical administration to the eye and provide for sustained release of ciprofloxacin.
  • polystyrene sulfonic acid polymers (and their salts) which are used in the formulations of the present invention have the following formula:
  • R H or CH ⁇
  • X an integer such that the molecular weight of the polystyrene sulfonic acid polymer may vary from about 10,000 to 1.6 million.
  • R is H and the molecular weight is between about 500,000 and 1,000,000, preferably about 600,000.
  • the polystyrene sulfonic acid polymers are used in the formulas of the present invention at a concentration less than about 8.0 percent by weight (wt%), preferably less than about 5.0 wt%.
  • Ciprofloxacin Ciprofloxacin, its preparation and use as an antimicrobial, are disclosed in U.S. Patent No. 4,670,444 (Grohe, et al.). The entire contents of that patent is incorporated herein by reference.
  • Ciprofloxacin has the following structure:
  • the chemical name for ciprofloxacin is l-cyclopropyl-6-fluoro-l,4-dihydro-4-oxo-7- (l-piperazinyl)-3-quinoline carboxylic acid.
  • the ciprofloxacin concentration in the formulations is less than or about 1.0 wt% of the total composition, preferably between about 0.1 wt% and 0.75 wt%.
  • the most preferred concentration is between about 0.2 and 0.4 wt%.
  • compositions of the present invention are prepared by combining the ciprofloxacin with the polystyrene sulfonic acid polymer in aqueous media and adjusting the pH, if necessary.
  • the compositions of the present invention may also include one or more ingredients conventionally found in ophthalmic or otic formulations, such as preservatives (e.g., benzalkonium chloride or thimerosal), viscosity-imparting agents (e.g., polyvinyl alcohol or hydroxypropylmethyl- cellulose), and toni ⁇ ty agents (e.g., sodium chloride or mannitol).
  • preservatives e.g., benzalkonium chloride or thimerosal
  • viscosity-imparting agents e.g., polyvinyl alcohol or hydroxypropylmethyl- cellulose
  • toni ⁇ ty agents e.g., sodium chloride or mannitol
  • compositions will also normally include buffering agents, such as phosphates and citrates, to maintain the pH within the range of physiological pH (pH between 6.0 and 7.5). Hydrochloric acid or sodium hydroxide will typically be used to adjust the pH of the resultant composition.
  • buffering agents such as phosphates and citrates
  • Hydrochloric acid or sodium hydroxide will typically be used to adjust the pH of the resultant composition.
  • the compositions are useful in treating ophthalmic and otic bacterial infections and are administered one to four times daily according to the discretion of a skilled clinician.
  • Ciprofloxacin HC1 Monohydrate 0.35*
  • Step 13 If batch weight is less than 99% of the weight measured in Step 10, adjust to the weight in Step 10 with Purified Water through the hydrophilic sterilizing filter. Mix to homogeneity (minimum of 15 minutes).

Landscapes

  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

L'invention porte sur des compositions pharmaceutiques aqueuses contenant une combinaison synergique de ciprofloxacine et d'un polymère d'acide polystyrène sulfonique. Ces compositions, qui se présentent sous la forme d'une solution limpide, sont d'une administration commode et sont à libération prolongée. L'invention porte également sur des modes d'emploi de ces compositions.
PCT/US1995/006587 1995-05-24 1995-05-24 Compositions antibacteriennes Ceased WO1996037191A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
PCT/US1995/006587 WO1996037191A1 (fr) 1995-05-24 1995-05-24 Compositions antibacteriennes
JP52719495A JP2944759B2 (ja) 1995-05-24 1995-05-24 抗菌性組成物
AU27621/95A AU705718B2 (en) 1995-05-24 1995-05-24 Antibacterial compositions

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US1995/006587 WO1996037191A1 (fr) 1995-05-24 1995-05-24 Compositions antibacteriennes

Publications (1)

Publication Number Publication Date
WO1996037191A1 true WO1996037191A1 (fr) 1996-11-28

Family

ID=22249170

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1995/006587 Ceased WO1996037191A1 (fr) 1995-05-24 1995-05-24 Compositions antibacteriennes

Country Status (3)

Country Link
JP (1) JP2944759B2 (fr)
AU (1) AU705718B2 (fr)
WO (1) WO1996037191A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000066126A3 (fr) * 1999-04-29 2001-04-05 Alza Corp Composition liposomique pour une retention medicamenteuse amelioree
EP2273989A4 (fr) * 2008-04-07 2013-05-01 Interface Biologics Inc Polythérapie pour le traitement des infections bactériennes

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5624281B2 (ja) * 2009-04-21 2014-11-12 東亜薬品株式会社 光安定性に優れたキノロン系抗菌薬含有液体製剤

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4670444A (en) * 1980-09-03 1987-06-02 Bayer Aktiengesellschaft 7-amino-1-cyclopropyl-4-oxo-1, 4-dihydro-quinoline-and naphthyridine-3-carboxylic acids and antibacterial agents containing these compounds
US5104649A (en) * 1988-05-11 1992-04-14 Monsanto Company Surface-functionalized biocidal polymers

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3142854A1 (de) * 1981-10-29 1983-05-11 Bayer Ag, 5090 Leverkusen 1-cyclopropyl-6-fluor-1,4-dihydro-4-oxo-7-piperazino-chinolin-3-carbonsaeuren, verfahren zu ihrer herstellung sowie diese enthaltende antibakterielle mittel
CA2064160C (fr) * 1991-03-27 1998-08-11 Paul J. T. Missel Emploi de polysaccharides gelifiants combines a des substrats finement divises a action de vecteur des medicaments, dans des compositions ophthalmiques a usage local

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4670444A (en) * 1980-09-03 1987-06-02 Bayer Aktiengesellschaft 7-amino-1-cyclopropyl-4-oxo-1, 4-dihydro-quinoline-and naphthyridine-3-carboxylic acids and antibacterial agents containing these compounds
US4670444B1 (en) * 1980-09-03 1999-02-09 Bayer Ag and-naphthyridine-3-carboxylic acids and antibacte7-amino-1-cyclopropyl-4-oxo-1,4-dihydro-quinoline-rial agents containing these compounds
US5104649A (en) * 1988-05-11 1992-04-14 Monsanto Company Surface-functionalized biocidal polymers

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000066126A3 (fr) * 1999-04-29 2001-04-05 Alza Corp Composition liposomique pour une retention medicamenteuse amelioree
EP2273989A4 (fr) * 2008-04-07 2013-05-01 Interface Biologics Inc Polythérapie pour le traitement des infections bactériennes

Also Published As

Publication number Publication date
AU2762195A (en) 1996-12-11
AU705718B2 (en) 1999-05-27
JP2944759B2 (ja) 1999-09-06
JPH09507679A (ja) 1997-08-05

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