WO2002004012A1 - Anhydrous pharmaceutical composition of vancomycin for topical use - Google Patents

Anhydrous pharmaceutical composition of vancomycin for topical use Download PDF

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Publication number
WO2002004012A1
WO2002004012A1 PCT/IB2001/001176 IB0101176W WO0204012A1 WO 2002004012 A1 WO2002004012 A1 WO 2002004012A1 IB 0101176 W IB0101176 W IB 0101176W WO 0204012 A1 WO0204012 A1 WO 0204012A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
anhydrous pharmaceutical
composition according
vancomycin
present
Prior art date
Application number
PCT/IB2001/001176
Other languages
French (fr)
Other versions
WO2002004012A8 (en
Inventor
Vincenzo De Tommaso
Original Assignee
Micio Pharma Chemical Ag
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 Micio Pharma Chemical Ag filed Critical Micio Pharma Chemical Ag
Priority to AU2001274420A priority Critical patent/AU2001274420A1/en
Publication of WO2002004012A1 publication Critical patent/WO2002004012A1/en
Publication of WO2002004012A8 publication Critical patent/WO2002004012A8/en

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
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/14—Peptides containing saccharide radicals; Derivatives thereof, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone

Definitions

  • the present invention refers to anhydrous pharmaceutical compositions of vancomycin for topical use.
  • Vancomycin is a glycopeptide antibiotic having a broad spectrum of antimicrobal activity, principally active against gram-positive bacteria. It inhibits the synthesis of the cell wall in sensitive bacteria by forming complexes with the mucopeptide precursors of this cell structure.
  • Vancomycin hydrochloride is a white powder, water soluble at concentration higher than 100 mg/ml and it is generally- administered intravenously, more rarely orally.
  • the pharmaceutical compositions of the present invention for topical use are useful for the treatment of dermal infections and furthermore they have the advantage of being very stabl .
  • the anhydrous pharmaceutical compositions for topical use of the present invention comprise: a) vancomycin, b) one or more glycols and/or the ethers thereof, c) one or more fatty acid triglycerides and /or the polyoxyethylene derivatives thereof, d) a gelling agent.
  • Vancomycin is present either in the form of the free base or of a pharmaceutically acceptable salt thereof, in particular as hydrochloride .
  • the glycols and/or the ethers thereof may preferably be ethylene glycol, propylene glycol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether.
  • the fatty acid triglicerides and /or the polyoxyethylene derivative thereof are preferably chosen in the group consisting of C 8 , C 10 ,C 12 ,C 14 , C 16 , C 18 , C 20 fatty acid triglicerides and the polyoxyethylene derivatives thereof wherein the polyoxyethylene has preferably a molecular weight from 200 to
  • Labrasol polyethylene glycol C 8 . 10 glycerides
  • the gelling agent preferably is a cellulose ester or ether, a polymer or copolymer of the acrylic or methacrylic acid, a polymer or copolymer of an acrylic or methacrylic acid ester, xanthan gum, carrageenin.
  • Vancomycin or a salt thereof is present in an amount varying from 0.01 to 25% by weight of the total composition.
  • the other ingredients are present in an amount varying from
  • the component b) preferably is present in an amount varying from 0.1 to 99% by weight of the total composition.
  • the component c) preferably is present in an amount varying from 0.01 to 30 % by weight of the total composition.
  • the component d) preferably is present in an amount varying from 0.01 to 15% by weight of the total composition.
  • compositions of the present invention may contain a surfactant which may be non-ionic, anionic or cationic.
  • Preferred cationic surfactants are the quaternary ammonium salts.
  • a preferred anionic surfactant is sodium lauryl sulfate.
  • a preferred non-ionic surfactant is polyoxyethylene stearyl ether.
  • compositions of the present invention may contain an emulsifying agent.
  • compositions of the present invention may be prepared by the usual methods known to a person skilled in the art .

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)

Abstract

The present invention refers to an anhydrous pharmaceutical composition of vancomycin, in the form of the free base or a pharmaceutically acceptable salt thereof, for topical use.

Description

ANHYDROUS PHARMACEUTICAL COMPOSITION OF VANCOMYCIN FOR
TOPICAL USE
The present invention refers to anhydrous pharmaceutical compositions of vancomycin for topical use.
Vancomycin is a glycopeptide antibiotic having a broad spectrum of antimicrobal activity, principally active against gram-positive bacteria. It inhibits the synthesis of the cell wall in sensitive bacteria by forming complexes with the mucopeptide precursors of this cell structure.
Vancomycin hydrochloride is a white powder, water soluble at concentration higher than 100 mg/ml and it is generally- administered intravenously, more rarely orally. The pharmaceutical compositions of the present invention for topical use are useful for the treatment of dermal infections and furthermore they have the advantage of being very stabl . The anhydrous pharmaceutical compositions for topical use of the present invention comprise: a) vancomycin, b) one or more glycols and/or the ethers thereof, c) one or more fatty acid triglycerides and /or the polyoxyethylene derivatives thereof, d) a gelling agent.
Vancomycin is present either in the form of the free base or of a pharmaceutically acceptable salt thereof, in particular as hydrochloride .
The glycols and/or the ethers thereof may preferably be ethylene glycol, propylene glycol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether. The fatty acid triglicerides and /or the polyoxyethylene derivative thereof are preferably chosen in the group consisting of C8, C10,C12,C14, C16 , C18 , C20 fatty acid triglicerides and the polyoxyethylene derivatives thereof wherein the polyoxyethylene has preferably a molecular weight from 200 to
10,000. Labrasol (polyethylene glycol C8.10 glycerides) is particularly preferred.
The gelling agent preferably is a cellulose ester or ether, a polymer or copolymer of the acrylic or methacrylic acid, a polymer or copolymer of an acrylic or methacrylic acid ester, xanthan gum, carrageenin.
Vancomycin or a salt thereof is present in an amount varying from 0.01 to 25% by weight of the total composition. The other ingredients are present in an amount varying from
0.01 to 99% by weight of the total composition.
The component b) preferably is present in an amount varying from 0.1 to 99% by weight of the total composition.
The component c) preferably is present in an amount varying from 0.01 to 30 % by weight of the total composition.
The component d) preferably is present in an amount varying from 0.01 to 15% by weight of the total composition.
Furthermore, the pharmaceutical compositions of the present invention may contain a surfactant which may be non-ionic, anionic or cationic.
Preferred cationic surfactants are the quaternary ammonium salts.
A preferred anionic surfactant is sodium lauryl sulfate.
A preferred non-ionic surfactant is polyoxyethylene stearyl ether.
Furthermore, the pharmaceutical compositions of the present invention may contain an emulsifying agent.
The pharmaceutical compositions of the present invention may be prepared by the usual methods known to a person skilled in the art .
EXAMPLE
1 Cream for topical use VANCOMYCIN (free base) 1.0 g
TRANSCUTOL 30.0 g
(diethylene glycol monomethyl ether)
PROPYLENE GLYCOL 60.0 g LAERASOL 5.5 g
(polyethylene glycol C8-ιo glicerides)
CARBOPOL 3.5 g
(acrylic acid copolymer)
The above reported amounts of Transcutol, Labrasol and propylene glycol were placed in a suitable tank. The above reported amount of carbopol was added to the mixture, which was then solubilized and homogenized in a turbomixer. The thus formed gel was cooled to 30°C and vancomycin was added thereto. Vancomycin was solubilized with the aid of a turbomixer while maintaining the temperature at 35-40°C. Plastic tubes were filled with the so obtained homogeneous gel up to a weight of 10 to 20g.

Claims

1) An anhydrous pharmaceutical composition of vancomycin, in the form of the free base or a pharmaceutically acceptable salt thereof, for topical use.
2) An anhydrous pharmaceutical composition according to claim 1 comprising: a) vancomycin, in the form of the free base or a pharmaceutically acceptable salt thereof, b) one or more glycols and/or the ethers thereof, c) one or more fatty acid triglicerides and /or the polyoxyethylene derivatives thereof, and d) a gelling agent .
3) An anhydrous pharmaceutical composition according to claim 1 or 2, wherein vancomycin is in the form of hydrochloride .
4) An anhydrous pharmaceutical composition according to claim 1 to 3 , wherein vancomycin is present in an amount varying from 0.01 to 25 % by weight of the total composition.
5) An anhydrous pharmaceutical composition according to claims 2 to 4 , wherein the component b) is present in an amount varying from 0.1 to 99 % by weight of the total composition. 6) An anhydrous pharmaceutical composition according to claims 2 to 5, wherein the component c) is present in an amount varying from 0.01 to 30 % by weight of the total composition.
7) An anhydrous pharmaceutical composition according to claims 2 to 6, wherein the component d) is present in an amount varying from 0.01 to 15 % by weight of the total composition. 8) An anhydrous pharmaceutical composition according to claims 2 to 7, wherein the glycols and/or the ethers thereof are chosen in the group consisting of ethylene glycol, propylene glycol, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether.
9) An anhydrous pharmaceutical composition according to claims 2 to 8, wherein the fatty acid triglicerides and /or their polyoxyethylene derivatives, are chosen in the group consisting of C8_2o fatty acid triglicerides and the polyoxyethylene derivatives thereof wherein the polyoxyethylene has preferably a molecular weight from 200 to 10,000.
10) An anhydrous pharmaceutical composition according to claims 2 to 9, wherein the gelling agent is chosen in the group consisting of cellulose esters or ethers, polymers or copolymers of the acrylic or methacrylic acid, polymers or copolymers of acrylic or methacrylic acid esters, xathan gum, carrageenin.
11) An anhydrous pharmaceutical composition according to claims 2 to 10, furthermore comprising a surfactant.
12) An anhydrous pharmaceutical composition according to claims claims 2 to 11, furthermore comprising an emulsifying agent.
PCT/IB2001/001176 2000-07-11 2001-07-03 Anhydrous pharmaceutical composition of vancomycin for topical use WO2002004012A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001274420A AU2001274420A1 (en) 2000-07-11 2001-07-03 Anhydrous pharmaceutical composition of vancomycin for topical use

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH13602000 2000-07-11
CH1360/00 2000-07-11

Publications (2)

Publication Number Publication Date
WO2002004012A1 true WO2002004012A1 (en) 2002-01-17
WO2002004012A8 WO2002004012A8 (en) 2002-04-04

Family

ID=4565412

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2001/001176 WO2002004012A1 (en) 2000-07-11 2001-07-03 Anhydrous pharmaceutical composition of vancomycin for topical use

Country Status (2)

Country Link
AU (1) AU2001274420A1 (en)
WO (1) WO2002004012A1 (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006118948A2 (en) * 2005-04-29 2006-11-09 Cubist Pharmaceuticals, Inc. Therapeutic compositions
US7527807B2 (en) 2000-06-21 2009-05-05 Cubist Pharmaceuticals, Inc. Compositions and methods for increasing the oral absorption of antimicrobials
EP2055309A1 (en) * 2007-10-31 2009-05-06 Pharmatex Italia Srl Vancomycin and Teicoplanin anhydrous formulations for topical use
US9241971B1 (en) 2014-07-18 2016-01-26 Kurobe, Llc Topical vancomycin formulation and methods of use
WO2018017814A1 (en) * 2016-07-20 2018-01-25 President And Fellows Of Harvard College Peptidoglycan glycosyltransferase inhibitors of sed proteins for treating bacterial infections
WO2022248744A1 (en) * 2021-05-28 2022-12-01 Fundación Gaiker Transcutol-polyol-active agent ternary complex, pharmaceutical composition for topical use comprising same, method for obtaining same and use thereof in different patologies
WO2023040397A1 (en) * 2021-09-14 2023-03-23 浙江普利药业有限公司 Vancomycin gel and preparation method therefor

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5314685A (en) * 1992-05-11 1994-05-24 Agouron Pharmaceuticals, Inc. Anhydrous formulations for administering lipophilic agents
US5681873A (en) * 1993-10-14 1997-10-28 Atrix Laboratories, Inc. Biodegradable polymeric composition
WO1999042083A1 (en) * 1998-02-20 1999-08-26 Kee Hung Hau Antibiotics in dry dosage forms for the treatment of shallow ulcers of the oral mucosa
WO2000033877A1 (en) * 1998-12-04 2000-06-15 Johnson And Johnson Consumer Companies, Inc. Anhydrous topical skin preparations
WO2001000226A1 (en) * 1999-06-29 2001-01-04 Toa Pharmaceutical Co., Ltd. Ophthalmic ointments for treating infective eye diseases
WO2001012128A2 (en) * 1999-08-18 2001-02-22 Atlantic Biomed Corporation Antibacterial agents for the treatment of acute mucosal infections

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5314685A (en) * 1992-05-11 1994-05-24 Agouron Pharmaceuticals, Inc. Anhydrous formulations for administering lipophilic agents
US5681873A (en) * 1993-10-14 1997-10-28 Atrix Laboratories, Inc. Biodegradable polymeric composition
WO1999042083A1 (en) * 1998-02-20 1999-08-26 Kee Hung Hau Antibiotics in dry dosage forms for the treatment of shallow ulcers of the oral mucosa
WO2000033877A1 (en) * 1998-12-04 2000-06-15 Johnson And Johnson Consumer Companies, Inc. Anhydrous topical skin preparations
WO2001000226A1 (en) * 1999-06-29 2001-01-04 Toa Pharmaceutical Co., Ltd. Ophthalmic ointments for treating infective eye diseases
WO2001012128A2 (en) * 1999-08-18 2001-02-22 Atlantic Biomed Corporation Antibacterial agents for the treatment of acute mucosal infections

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CORBETT, J. ET AL: "Injectable, absorbable gel -formers for controlled release of antibiotics", PROC. INT. SYMP. CONTROLLED RELEASE BIOACT. MATER. (1998), 25TH, 38-39, XP001013454 *
DATABASE CHEMICAL ABSTRACTS *
SVINHUFVUD, LILLEMOR BORTHEN ET AL: "Effect of topical administration of vancomycin versus chlorhexidine on.alpha.-hemolytic streptococci in oral cavity", ORAL SURG., ORAL MED., ORAL PATHOL. (1988), 66(3), 304-9, XP001013385 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7527807B2 (en) 2000-06-21 2009-05-05 Cubist Pharmaceuticals, Inc. Compositions and methods for increasing the oral absorption of antimicrobials
US8303989B2 (en) 2000-06-21 2012-11-06 International Health Management Associates, Inc. Compositions and methods for increasing the oral absorption of antimicrobials
WO2006118948A2 (en) * 2005-04-29 2006-11-09 Cubist Pharmaceuticals, Inc. Therapeutic compositions
WO2006118948A3 (en) * 2005-04-29 2007-05-18 Cubist Pharm Inc Therapeutic compositions
US8968781B2 (en) 2005-04-29 2015-03-03 Cubist Pharmaceuticals, Inc. Therapeutic compositions
EP2055309A1 (en) * 2007-10-31 2009-05-06 Pharmatex Italia Srl Vancomycin and Teicoplanin anhydrous formulations for topical use
WO2009056547A1 (en) * 2007-10-31 2009-05-07 Pharmatex Italia Srl Vancomycin and teicoplanin anhydrous formulations for topical use
US20100267624A1 (en) * 2007-10-31 2010-10-21 Vincenzo De Tommaso Vancomycin and teicoplanin anhydrous formulations for topical use
US9241971B1 (en) 2014-07-18 2016-01-26 Kurobe, Llc Topical vancomycin formulation and methods of use
WO2018017814A1 (en) * 2016-07-20 2018-01-25 President And Fellows Of Harvard College Peptidoglycan glycosyltransferase inhibitors of sed proteins for treating bacterial infections
WO2022248744A1 (en) * 2021-05-28 2022-12-01 Fundación Gaiker Transcutol-polyol-active agent ternary complex, pharmaceutical composition for topical use comprising same, method for obtaining same and use thereof in different patologies
WO2023040397A1 (en) * 2021-09-14 2023-03-23 浙江普利药业有限公司 Vancomycin gel and preparation method therefor

Also Published As

Publication number Publication date
AU2001274420A1 (en) 2002-01-21
WO2002004012A8 (en) 2002-04-04

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