GB2202743A - Antifungals - Google Patents

Antifungals Download PDF

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Publication number
GB2202743A
GB2202743A GB8807788A GB8807788A GB2202743A GB 2202743 A GB2202743 A GB 2202743A GB 8807788 A GB8807788 A GB 8807788A GB 8807788 A GB8807788 A GB 8807788A GB 2202743 A GB2202743 A GB 2202743A
Authority
GB
Grant status
Application
Patent type
Prior art keywords
composition
nitrate
weight
glycol
water
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.)
Granted
Application number
GB8807788A
Other versions
GB8807788D0 (en )
GB2202743B (en )
Inventor
Jean-Pierre Laugier
Beatrice Renault
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.)
L'Oreal SA
Original Assignee
L'Oreal SA
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

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K8/00Cosmetics or similar toilet preparations
    • A61K8/18Cosmetics or similar toilet preparations characterised by the composition
    • A61K8/30Cosmetics or similar toilet preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494Cosmetics or similar toilet preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4946Imidazoles or their condensed derivatives, e.g. benzimidazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4151,2-Diazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILET PREPARATIONS
    • A61Q3/00Manicure or pedicure preparations

Description

ANTIFUNGAL COMPOSITION 2 J2 0 2 7 4 3 The present invention relates to an

antifungal composition comprising miconazole nitrate or econazole nitrate which may be used in the treatment of fungal infections of the nails and/or the surrounding tissues.

tl, Both miconazole nitrate and econazole nitrate are imidazole derivatives having good antifungal and antibacterial activity. They are especially recommended in the local treatment of candidiasis, dermatophytosis, pityriasis versicolor and onychomycosis.

The galenical forms hitherto proposed based on miconazole nitrate or econazole nitrate do not provide good bioavailability of the active principle since it is in suspension in the crystalline state. In order to provide improved bioavailability, solutions of the imidozale derivatives in fatty excipients, in particular in undecylenic acid, which improves their solubility, have been proposed in EP-A-0,064,830. However, such solutions are still not satisfactory as they are anhydrous, and consequently do not hydrate the nail. This reduces the bioavailability of the active principle.

Since both miconazole nitrate and econazole nitrate are insoluble in water and only very slightly soluble in an aqueous-alcoholic mixture, it has not hitherto been possible to obtain antifungal compositions containingthese active substances in aqueous solution at concentrations that are adequate to provide a good therapeutic effect.

The presence of water confers a particular advantage since it hydrates the nail so that the active principle can be delivered at a deep level.

We have surprisingly found that it is possible to obtain antifungal compositions containing miconazole nitrate or econazole nitrate in aqueous solution, by using urea as a solubilizing agent. The urea in an aqueous solution significantly increases the solubility of the miconazole nitrate and the econazole nitrate.

The present invention therefore provides an antifungal composition suitable for topical application comprising at least 1% by weight, relative to the total weight of the composition, of miconazole nitrate or econazole nitrate dissolved in a mixture of water, urea and a watersoluble dissolving intermediary, the weight of urea. present not exceeding the weight of water present.

The composition may, for example, be in the form of a lotion, gel (a thickened composition) or varnish.

The urea increases the solubility of the miconazole nitrate or the econazole nitrate irrespective of the nature of the water-soluble dissolving intermediary used for the formation of the aqueous phase.

The miconazole nitrate or the econazole nitrate is preferably present, in the dissolved state, in an amount of from 1 to 2% by weight relative to the total weight of the composition.

The water is generally present in an amount of from 5 to 20% by weight, and the urea is generally present in an amount of from 1 to 20%, relative to the total weight of the composition.

The dissolving intermediary can be, for example, a primary or secondary alcohol, a ketone, a glycol or a glycol ether, or a mixture thereof.

The dissolving intermediary should not only be water-soluble, but also, in the case of varnishes, be capable of solubilizing a film-forming resin to leave a film after evaporation and/or penetration.

Examples of primary or secondary alcohols are methanol, ethanol, isopropanol, n-propanol and benzyl alcohol. Suitable ketones are acetone, diethyl ketone, diisobutyl ketone, ethyl butyl ketone, methyl isobutyl ketone and methyl propyl ketone. Examples of glycols and glycol ethers are ethylene glycol, propylene glycol, diethylene glycol, dipropylene glycol, ethylene glycol methyl ether, ethylene glycol ethyl ether and diethylene glycol methyl ether.

According to a preferred embodiment of the invention, the dissolving intermediary is ethanol or a mixutre of ethanol and propylene glycol.

When the composition is in the form of a gel, it contains a thickening or gelling agent such as a montmorillonite derivative, bentonite derivative, bentone, hectorite, kaolin, attapulgite, hydroxypropyl-guar, a cellulose derivative such as methyl cellulose, hydroxymethylcellulose, hydroxybutylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, methylhydroxyethylcellulose or methylhydroxypropylcellulose, or a crosslinked polyacrylic acid such as that sold by Goodrich under the name CARBOPOL (Trade Mark).

The thickening or gelling agent is preferably present in an amount of from 0.5 to 2%, more preferably from 0.7 to 1.5%, by weight relative to the total weight of the composition.

When the composition is in the form of a varnish, it contains a resin which leaves a film remaining after evaporation of the solvent. Any polymer or copolymer compatible with the solvent may be used, for example, the polyvinylpyrrolidone/vinyl acetate polymer sold by Gaf Corporation under the name OPVP-VA E335", the polyvinyl acetate sold by Rhone-Poulenc under the name Rhodopas M60A (Trade Mark), the polyacrylamide sold by American Cyanamid under the name Gelamide 250 (Trade Mark), the hydroxymethylcellulose phthalate sold by Seppic under the name "HP55", the dimethylaminomethyl methacrylate/lower alkyl methacrylate sold by Rohm and Haas under the name Eudragit E100 (Trade Mark), the vinyl acetate/crotonic acid copolymer sold by National Starch under the name "Resin 28-1310", the methyl vinyl ether/butyl monomaleate copolymer sold by Gaf Corporation under the name 0Gantrez ES 425" (Trade Mark) and a polymer based on alkyl acrylate or 11 methacrylate and acrylic or methacrylic acid.

The resin is generally present in an amount of from 7.5 to 30%, preferably from 10 to 20%, relative to the total weight of the composition.

The composition can, in addition, comprise other ingredients such as preservatives, antioxidants and, in the case of varnishes, plasticizers such as glycerol.

The present invention also provides an antifungal composition as defined above for use in a method of treatment of the human or animal body by therapyr in particular for use in the treatment of fungal infections of the nails or of the surrounding tissue.

The invention is now further described in the following Examples showing suitable antifungal compositions of the invention.

E ample I Varnish:

Miconazole nitrate 2 % Water.... 0 0 9.5 % Urea 9 Absolute ethanol 25.5 % Acetone 14 % Polymer PVP-VA E 335 sold by the company GAF (50% strength solution 40 Example' II Gel:

Econazole nitrate.......................... Water......................... ............. Urea....................................... Propylene glycol............................ Absolute ethanol....................... ..... Hydroxypropylcellulose sold by the company HERCULES under the name "KLUCEL H" Example III Lotion:

Miconazole nitrate.......................... Water........................ ............... Urea....................................... Propylene glycol............................ Absolute ethanol....................... ..... Example IV Varnish:

Miconazol.e nitrate.......................... Water....................... ................ Urea........................................ Absolute ethanol............................ Glycerol.............................. ...... Dimethylaminoethyl methacrylate/lower alkyl methacrylate polymer sold by the company ROBM and HAAS under the name "Eudragit E 100n......... ...................

1 1 43 43 1 1 43 2 10 64 2 12 1

Claims (15)

  1. An antifungal composition suitable for topical application comprising at least 1% by weight, relative to the total weight of the composition, of miconazole nitrate or econazole nitrate dissolved in a mixture of water, urea and a water-soluble dissolving intermediary, the weight of urea present not exceeding the,weight of water present.
  2. 2. A composition according to claim 1 which comprises from 1 to 2% by weight, relative to the total weight of the composition, of the miconazole nitrate or the econazole nitrate dissolved in the mixture of water, urea and a water-soluble dissolving intermediary.
  3. 3. A composition according to claim 1 or 2 wherein the water is present in an amount of from 5 to 20% by weight relative to the total weight of the composition.
  4. 4. A composition according to any one of claims 1 to 3 wherein the urea is present in an amount of from 1 to 20% by weight relative to the total weight of the composition.
  5. 5. A composition according to any one of claims 1 to 4 wherein the dissolving intermediary is a primary or secondary alcohol, a ketone, a glycol or a glycol ether.
  6. 6. A compostion according to claim 5 wherein the primary or secondary alcohol is methanol, ethanol, isopropanol, n-propanol or benzyl alcohol.
  7. 7. A composition according to claim 5 wherein the ketone is acetone, diethyl ketone, diisobutyl ketone, ethyl butyl ketone, methyl isobutyl ketone or methyl propyl ketone.
  8. 8. A composition according to claim 5 wherein the glycol or glycol ether is ethylene glycol, propylene glycol, diethylene glycol, dipropylene glycol, ethylene glycol methyl ether, ethylene glycol ethyl ether or d. iethylene glycol methyl ether.
  9. 9. A composition according to claim 6 wherein the dissolving intermediary is ethanol or a mixture of ethanol and propylene glycol.
  10. 10. A composition according to any one of claims 1 to 9 which is in the form of a lotion, gel or varnish.
  11. 11. A composition according to claim 10 which also comprises a thickening or gelling agent in an amount of from 0.5 to 2% by weight relative to the total weight of the composition.
  12. 12. A composition according to claim 10 which also comprises a resin in amount of from 7.5 to 30% by weight relative to the total weight of the composition.
  13. 13. An antifungal c'omposition substantially as described in any one of Examples I to IV.
  14. 14. An antifungal composition as defined in any one of claim 1 to 13 for use in a method of treatment of the human or animal body by therapy.
  15. 15. An antifungal composition as defined in any one of claims 1 to 13 for use in the treatment of fungal infections of the nails or of the surrounding tissue.
    Published 1988 at The Patent Office, State House, 66171 High Holborn, London WC1R 4TP. Further copies may be obtained from The Patent Office, Sales Bran ch, St Mary Cray, Orpington, Eent BR5 3RD. Printed by Multiplex techniques ltd, St Mary Cray, Kent. Con. 1187.
GB8807788A 1987-04-01 1988-03-31 Topical antifungal composition Expired - Fee Related GB2202743B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
FR8704560A FR2613227B1 (en) 1987-04-01 1987-04-01 Pharmaceutical compositions based miconazole nitrate or econazole nitrate in the treatment of fungal nail infections

Publications (3)

Publication Number Publication Date
GB8807788D0 GB8807788D0 (en) 1988-05-05
GB2202743A true true GB2202743A (en) 1988-10-05
GB2202743B GB2202743B (en) 1990-11-21

Family

ID=9349669

Family Applications (1)

Application Number Title Priority Date Filing Date
GB8807788A Expired - Fee Related GB2202743B (en) 1987-04-01 1988-03-31 Topical antifungal composition

Country Status (4)

Country Link
JP (1) JPS63258814A (en)
DE (1) DE3810897A1 (en)
FR (1) FR2613227B1 (en)
GB (1) GB2202743B (en)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0389778A1 (en) * 1989-02-24 1990-10-03 F. Hoffmann-La Roche Ag Nail Varnish
EP0565072A1 (en) * 1992-04-10 1993-10-13 Esparma Pharmazeutische Fabrik GmbH Nail lacquer for the treatment of onychomycoses
WO1995003775A1 (en) * 1993-07-28 1995-02-09 Pfizer Inc. Antifungal nail solution
US5422366A (en) * 1991-12-18 1995-06-06 Advanced Oxygen Technologies, Inc. Treatment of fungal infections
US5464610A (en) * 1992-10-15 1995-11-07 Schering-Plough Healthcare Products, Inc. Method for treating onychomycosis
US6143794A (en) * 1998-04-17 2000-11-07 Bertek Pharmaceuticals, Inc. Topical formulations for the treatment of nail fungal diseases
EP1138314A2 (en) * 2000-03-27 2001-10-04 Taro Pharmaceutical Industries Ltd Controlled delivery system of antifungal and keratolytic agents for local treatment of fungal infections of the nail and surrounding tissues
EP1635770A2 (en) * 2003-03-21 2006-03-22 Nexmed Holdings, Inc. Antifungal nail coat and method of use
US7476396B2 (en) 2001-05-30 2009-01-13 Sanofi-Aventis Deutschland Gmbh Composition for removing abnormal keratinous material
US8257688B2 (en) 2000-03-27 2012-09-04 Taro Pharmaceuticals Industries Controlled delivery system of antifungal and keratolytic agents for local treatment of fungal infections of the nail and surrounding tissues
CN105496958A (en) * 2015-12-24 2016-04-20 广东同德药业有限公司 Econazole nitrate spray and preparation method thereof
US9579297B2 (en) 2005-12-28 2017-02-28 Teikoku Seiyaku Co., Ltd. Pharmaceutical composition for application to nail

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2844197B1 (en) 2002-09-05 2006-06-23 Galderma Res & Dev Solution for ungual and peri-ungeale
WO2004021968A3 (en) * 2002-09-05 2004-05-27 Agnes Ferrandis Solution for ungual application
EP1557375A1 (en) * 2004-01-23 2005-07-27 Neubourg Skin Care GmbH & Co. KG Spray dispenser for nail tincture
EP1767247B1 (en) * 2005-09-26 2008-11-26 Faber-Castell AG Liquid cosmetic composition for colouring the nails and the skin
FR2937250B1 (en) * 2008-10-21 2013-05-10 Fabre Pierre Dermo Cosmetique film-forming solution based urea for the treatment of nail psorasis
WO2010108060A8 (en) * 2009-03-20 2011-11-03 Stiefel Laboratories, Inc. Fatty acid monoglyceride compositions

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2116425A (en) * 1982-03-19 1983-09-28 Roehm Pharma Gmbh Antimycotic preparations in a cream or ointment base

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2542616B1 (en) * 1983-03-17 1987-07-31 Unilever Nv Composition for the treatment of mucous membranes based on an antibiotic and a gel forming hydrocolloid
US4912124A (en) * 1984-02-23 1990-03-27 Ortho Pharmaceutical Corporation Antifungal dermatological solution

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2116425A (en) * 1982-03-19 1983-09-28 Roehm Pharma Gmbh Antimycotic preparations in a cream or ointment base

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0389778A1 (en) * 1989-02-24 1990-10-03 F. Hoffmann-La Roche Ag Nail Varnish
US5120530A (en) * 1989-02-24 1992-06-09 Hoffmann-La Roche Inc. Antimicotic nail varnish containing amorolfine in quaternary ammonium acrylic copolymer
US5422366A (en) * 1991-12-18 1995-06-06 Advanced Oxygen Technologies, Inc. Treatment of fungal infections
EP0565072A1 (en) * 1992-04-10 1993-10-13 Esparma Pharmazeutische Fabrik GmbH Nail lacquer for the treatment of onychomycoses
US5346692A (en) * 1992-04-10 1994-09-13 Roehm Pharma Gmbh Nail lacquer for the treatment of onychomycosis
US5464610A (en) * 1992-10-15 1995-11-07 Schering-Plough Healthcare Products, Inc. Method for treating onychomycosis
WO1995003775A1 (en) * 1993-07-28 1995-02-09 Pfizer Inc. Antifungal nail solution
US6143794A (en) * 1998-04-17 2000-11-07 Bertek Pharmaceuticals, Inc. Topical formulations for the treatment of nail fungal diseases
US7678366B2 (en) 2000-03-27 2010-03-16 Taro Pharmaceutical Industries Limited Controlled delivery system of antifungal and keratolytic agents for local treatment of fungal infections of the nail and surrounding tissues
EP1138314A3 (en) * 2000-03-27 2004-01-02 Taro Pharmaceutical Industries Ltd Controlled delivery system of antifungal and keratolytic agents for local treatment of fungal infections of the nail and surrounding tissues
EP1138314A2 (en) * 2000-03-27 2001-10-04 Taro Pharmaceutical Industries Ltd Controlled delivery system of antifungal and keratolytic agents for local treatment of fungal infections of the nail and surrounding tissues
US7074392B1 (en) 2000-03-27 2006-07-11 Taro Pharmaceutical Industries Limited Controllled delivery system of antifungal and keratolytic agents for local treatment of fungal infections
US8257688B2 (en) 2000-03-27 2012-09-04 Taro Pharmaceuticals Industries Controlled delivery system of antifungal and keratolytic agents for local treatment of fungal infections of the nail and surrounding tissues
US7476396B2 (en) 2001-05-30 2009-01-13 Sanofi-Aventis Deutschland Gmbh Composition for removing abnormal keratinous material
EP1635770A2 (en) * 2003-03-21 2006-03-22 Nexmed Holdings, Inc. Antifungal nail coat and method of use
EP2106805A1 (en) * 2003-03-21 2009-10-07 Nexmed Holdings, Inc. Antifungal nail coat and method of use
US7462362B2 (en) 2003-03-21 2008-12-09 Nexmed Holdings, Inc. Antifungal nail coat and method of use
EP1635770A4 (en) * 2003-03-21 2007-12-26 Nexmed Holdings Inc Antifungal nail coat and method of use
US9579297B2 (en) 2005-12-28 2017-02-28 Teikoku Seiyaku Co., Ltd. Pharmaceutical composition for application to nail
CN105496958A (en) * 2015-12-24 2016-04-20 广东同德药业有限公司 Econazole nitrate spray and preparation method thereof

Also Published As

Publication number Publication date Type
FR2613227B1 (en) 1990-12-28 grant
DE3810897A1 (en) 1988-10-20 application
GB8807788D0 (en) 1988-05-05 grant
FR2613227A1 (en) 1988-10-07 application
GB2202743B (en) 1990-11-21 grant
JPS63258814A (en) 1988-10-26 application

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Legal Events

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PCNP Patent ceased through non-payment of renewal fee

Effective date: 19930331