WO1999012520A1 - Compositions adaptees pour un sejour prolonge dans le rhino-pharynx - Google Patents

Compositions adaptees pour un sejour prolonge dans le rhino-pharynx Download PDF

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Publication number
WO1999012520A1
WO1999012520A1 PCT/EP1998/005716 EP9805716W WO9912520A1 WO 1999012520 A1 WO1999012520 A1 WO 1999012520A1 EP 9805716 W EP9805716 W EP 9805716W WO 9912520 A1 WO9912520 A1 WO 9912520A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition according
nasal
fatty acid
alcohol
ester
Prior art date
Application number
PCT/EP1998/005716
Other languages
English (en)
Inventor
Anthony Guy Hatton
Jane Elizabeth Hilton
Hugh Purdie Scott
Teresita Regina Geradine Tallon
Original Assignee
Smithkline Beecham Plc
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
Priority claimed from GBGB9719203.3A external-priority patent/GB9719203D0/en
Priority claimed from GBGB9806685.5A external-priority patent/GB9806685D0/en
Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Priority to JP2000510419A priority Critical patent/JP2001515850A/ja
Priority to CA002303443A priority patent/CA2303443A1/fr
Priority to EP98948935A priority patent/EP1033969A1/fr
Publication of WO1999012520A1 publication Critical patent/WO1999012520A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0043—Nose
    • 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
    • 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

Definitions

  • the present invention relates to a novel composition for nasal administration of medicaments.
  • the nasal passages may be used as a route of administration, for instance an ointment such as Bactroban Nasal may be applied to the anterior nares of the nose for a local topical effect.
  • Spray formulations may applied to the nostrils.
  • medicaments may administered to the lungs via the nostrils, using an aerosol or nebuliser.
  • the nasal passages comprise mucosal tissues which might be used as means of systemically delivering a medicament. Such local topical or systemic delivery would be enhanced if the formulation was to have a prolonged residence time in the nasal passages.
  • the present invention provides for a composition adapted for prolonged residence in the nasal passage, in particular the nasal pharynx, consisting essentially of:
  • the composition of this invention provides a low viscosity cream that is easy to administer and which readily changes in consistency and softens in the temperature conditions of the nose. Accordingly when inserted into the upper regions of the nose it can be transported deeper into the nasal passages by natural processes.
  • the composition is intended to be in the form of an oil-in-water cream emulsion.
  • the amounts of the components within the above ranges must be selected for individual components by routine trials to ensure that an oil-in-water emulsion is obtained.
  • the fatty acid triglycerides are typically vegetable (i.e. plant-derived) oils, such as coconut oil, sesame oil or soya bean oil.
  • An especially suitable vegetable oil is one that has to been fractionated so that it is predominantly medium chain length triglycerides.
  • Suitable medium-chain fatty acid triglycerides for use in the present invention may be of natural, semi-synthetic or synthetic origin and may include blends of different medium chain fatty acid triglycerides.
  • the term "medium-chain fatty acid” as used herein refers to a fatty acid having from 6 to 12, preferably 8 to 10 carbon atoms which may be branched or unbranched, preferably unbranched and which may be optionally substituted.
  • the triglyceride suitably comprises from 50 to 100% (w/w) of caprylic (Cg) acid and from 0 to 50% (w/w) of capric (Cio) ac id triglycerides.
  • Suitable examples include those available under the trade names MYRITOL; CAPTEX (Karlshams Lipid Specialties, Columbus OH), for instance CAPTEX 355, CAPTEX 300, CAPTEX 350, CAPTEX 850 and CAPTEX 8000; MIGLYOL (BASF), for instance the grades MIGLYOL 810, MIGLYOL 812 AND MIGLYOL 818 (which also comprises a linoleic acid triglyceride) and MAZOL 1400 (Mazer Chemical, Guernee, II).
  • the fatty acid content of representative products is: CAPTEX 355TM - CAPROIC ACID (2%), CAPRYLIC ACID (55%) and capric acid (42%); CAPTEX 8000 - at least 98% caprylic acid, MYGOL 810 - caproic acid (2%), caprylic acid (65-75%), capric acid (25-35%) and MIGLYOL 812 - caproic acid (3%), caprylic acid (50-65%), capric acid (30-45%) and lauric acid (5%) (manufacturer's data).
  • the polyoxyethylene ether or ester used in this invention is one which will function as a non-ionic surfactant.
  • suitable materials include polyoxyethylene glycol monocetyl ethers, such as Cetomacrogol 1000.
  • suitable non-ionic surfactants include: (a) polyoxyethylene fatty acid esters, for example polyoxyethylene stearic acid esters of the type available under the trade name MYRJ (ICI Americas, Inc.), for instance the product MYRJ 52 (a polyoxyethylene 40 stearate);
  • polyoxyetheylene-sorbitan fatty acid esters for example the mono- and tri-lauryl, palmityl, stearyl and oleyl esters, for instance the polyoxyethylene sorbitan monooleates available under the trade name of TWEEN (ICI Americas Inc.), such as TWEEN 20, 21, 40, 60, 61, 65, 80, 81 and 85, of which class TWEEN 80 is especially preferred;
  • polyoxyethylene glycol long-chain alkyl ethers such as polyoxyethylated glycol lauryl ether
  • polyoxyethylene glycol long-chain alkyl esters such as PEG-monostearate
  • the surfactant preferably has an HLB value in the range of 13 to 20.
  • fatty alcohol or ester there may be used any of such materials conventionally used in pharmaceutical or veterinary compositions such as stearyl alcohol, cetyl alcohol, cetyl stearyl alcohol, myristyl alcohol and glycerin monostearate.
  • cetostearyl alcohol is used, or a mixture of stearyl alcohol and cetyl alcohol.
  • a particularly preferred vehicle composition comprises fractionated coconut oil (typically about 55 to 60, especially about 57, parts by weight); polyoxyethylene glycol monocetyl ether (typically about 2 to 4, especially about 3, parts by weight); cetostearyl alcohol (typically about 2 to 4, especially about 3, parts by weight); with water for emulsification, and also preservatives, and flavourings if desired.
  • Typical preservatives include benzyl alcohol and phenoxyethanol.
  • composition of the present invention is particularly suitable for nasal administration.
  • the prolonged residence time of formulations of the present invention in the nasal passages, especially the nasal pharynx, makes them particularly suitable for topical treatment with local action or, since it provides prolonged contact of the formulation with an absorptive region, systemic delivery of a medicament.
  • Suitable medicaments include antibiotics, for instance mupirocin or a pharmaceutically acceptable salt or ester thereof.
  • compositions of the present invention may be used to treat a range of conditions, for instance a topically effective antibiotic such as mupirocin or a pharmaceutically acceptable salt or ester thereof, may be used to treat recurrent sinusitis or recurrent otitis media.
  • a topically effective antibiotic such as mupirocin or a pharmaceutically acceptable salt or ester thereof
  • Suitable pharmaceutically acceptable salts of mupirocin are well known in the art and include alkali metal salts such as sodium and lithium and alkaline earth metal salts such as calcium, of which the calcium salt is preferred, in particular the crystalline dihydrate from thereof described in EP 0 167 856-A (Beecham Group).
  • alkali metal salts such as sodium and lithium
  • alkaline earth metal salts such as calcium
  • Other suitable salts include silver and aluminium salts and ammonium and substituted- ammonium salts.
  • the salts may be anhydrous or may be in the form of pharmaceutically acceptable solvates, for instance alcoholates and, especially, hydrates.
  • Preferred salts include the calcium, silver and lithium salts, in particular the calcium salt.
  • the crystalline salt is preferably used, especially the crystalline hydrated calcium salt, more preferably the crystalline dihydrate salt.
  • Suitable pharmaceutically acceptable esters of mupirocin are well known in the art and include lower alkyl esters, especially the methyl and ethyl esters.
  • the mupirocin is preferably present as a finely divided powder. This may be achieved by milling, and most suitably by micronising (fluid energy milling) so that the medicament has a particle size less than 100 ⁇ m, preferably less than 10 ⁇ m.
  • a medicament for instance an antibiotic
  • an antibiotic is used at between 2 and 8%, typically about 4 to 6%, by weight of the formulation.
  • a relatively high dosage level to reduce the risk of the development of bacterial resistance.
  • the antibiotic is preferably present at a relatively high loading compared to other topical administration formulations.
  • composition of the invention may typically be administered into the nasal passages by a pump, such as an air lift pump. This may be adapted for nasal administration by addition of a modified nozzle.
  • composition of this invention may be produced by conventional pharmaceutical techniques.
  • the components of the carrier may be blended by mixing together at an elevated temperature until an emulsion has formed.
  • the mixture may then be cooled to room temperature, and, after the addition of any further optional ingredients, stirred to ensure adequate dispersion.
  • the antibiotic may be added during hot preparation of the base, or may be added with additional ingredients after cooling of the base. If necessary the composition may be provided in sterile condition.
  • Optional ingredients that may be added if desired include colourings and flavourings.
  • the invention is illustrated by the following Example.
  • An oil-in-water emulsion cream was prepared from the following:

Abstract

L'invention concerne des compositions destinées à l'administration d'un médicament, ces compositions étant adaptées pour un séjour prolongé dans les voies nasales, notamment dans le rhino-pharynx.
PCT/EP1998/005716 1997-09-11 1998-09-03 Compositions adaptees pour un sejour prolonge dans le rhino-pharynx WO1999012520A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP2000510419A JP2001515850A (ja) 1997-09-11 1998-09-03 鼻腔咽頭中の長期滞留に適合した組成物
CA002303443A CA2303443A1 (fr) 1997-09-11 1998-09-03 Compositions adaptees pour un sejour prolonge dans le rhino-pharynx
EP98948935A EP1033969A1 (fr) 1997-09-11 1998-09-03 Compositions adaptees pour un sejour prolonge dans le rhino-pharynx

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GBGB9719203.3A GB9719203D0 (en) 1997-09-11 1997-09-11 Novel composition and use
GBGB9806685.5A GB9806685D0 (en) 1998-03-26 1998-03-26 Novel composition
GB9719203.3 1998-03-27
GB9806685.5 1998-03-27

Publications (1)

Publication Number Publication Date
WO1999012520A1 true WO1999012520A1 (fr) 1999-03-18

Family

ID=26312214

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/005716 WO1999012520A1 (fr) 1997-09-11 1998-09-03 Compositions adaptees pour un sejour prolonge dans le rhino-pharynx

Country Status (4)

Country Link
EP (1) EP1033969A1 (fr)
JP (1) JP2001515850A (fr)
CA (1) CA2303443A1 (fr)
WO (1) WO1999012520A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1537857A1 (fr) * 2003-12-03 2005-06-08 Agis Industries (1983) Ltd Compositions à usage topique comprenant de la mupirocine, procédé de préparation et applications.

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2641605A1 (fr) * 2006-02-09 2007-08-23 Schering Corporation Formulations pharmaceutiques
EP2444067A1 (fr) * 2010-10-20 2012-04-25 Laboratorios Ojer Pharma S.L. Gel anhydrique comprenant muciprocin

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0069423A1 (fr) * 1981-07-02 1983-01-12 Yamanouchi Europe B.V. Composition pour application topique au corps
US4717720A (en) * 1985-04-11 1988-01-05 Centre International De Recherches Dermatologiques (C.I.R.D.) Benzonaphthalene derivatives and compositions
US4790989A (en) * 1986-06-26 1988-12-13 Beecham Group P.L.C. Treatment of fungal infections
US4879284A (en) * 1985-04-15 1989-11-07 L'oreal Naphthalene derivatives having retinoid type action, the process for preparation thereof and medicinal and cosmetic compositions containing them
WO1995010999A1 (fr) * 1993-10-22 1995-04-27 Smithkline Beecham Corporation Nouvelle composition

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0069423A1 (fr) * 1981-07-02 1983-01-12 Yamanouchi Europe B.V. Composition pour application topique au corps
US4717720A (en) * 1985-04-11 1988-01-05 Centre International De Recherches Dermatologiques (C.I.R.D.) Benzonaphthalene derivatives and compositions
US4879284A (en) * 1985-04-15 1989-11-07 L'oreal Naphthalene derivatives having retinoid type action, the process for preparation thereof and medicinal and cosmetic compositions containing them
US4790989A (en) * 1986-06-26 1988-12-13 Beecham Group P.L.C. Treatment of fungal infections
WO1995010999A1 (fr) * 1993-10-22 1995-04-27 Smithkline Beecham Corporation Nouvelle composition

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1537857A1 (fr) * 2003-12-03 2005-06-08 Agis Industries (1983) Ltd Compositions à usage topique comprenant de la mupirocine, procédé de préparation et applications.

Also Published As

Publication number Publication date
CA2303443A1 (fr) 1999-03-18
EP1033969A1 (fr) 2000-09-13
JP2001515850A (ja) 2001-09-25

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