WO2012061920A1 - Compositions de sels d'acide organique pour administration locale adaptées au traitement des infections - Google Patents

Compositions de sels d'acide organique pour administration locale adaptées au traitement des infections Download PDF

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Publication number
WO2012061920A1
WO2012061920A1 PCT/CA2010/001812 CA2010001812W WO2012061920A1 WO 2012061920 A1 WO2012061920 A1 WO 2012061920A1 CA 2010001812 W CA2010001812 W CA 2010001812W WO 2012061920 A1 WO2012061920 A1 WO 2012061920A1
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WIPO (PCT)
Prior art keywords
composition
sodium
propionate
zinc
acid salts
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PCT/CA2010/001812
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English (en)
Inventor
Peter Mladenovich
William D. Lougheed
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bioCEPTA Corporation
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Application filed by bioCEPTA Corporation filed Critical bioCEPTA Corporation
Priority to CA2834381A priority Critical patent/CA2834381A1/fr
Priority to US13/884,927 priority patent/US20140142177A1/en
Priority to PCT/CA2010/001812 priority patent/WO2012061920A1/fr
Priority to EP10859588.5A priority patent/EP2637654A4/fr
Publication of WO2012061920A1 publication Critical patent/WO2012061920A1/fr

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    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61P31/10—Antimycotics
    • 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
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses

Definitions

  • the present invention relates to non-aqueous topical compositions of low molecular weight, hydrophilic carboxylic acid salts and/or derivatives for treating toe and finger nail fungal infections (onychomycosis), as well as fungal infections of the skin.
  • Tinea pedis athletee's foot
  • Tinea unguium noil infections
  • Tinea cruris jock itch
  • Tinea corporis Tinea versicolor
  • Tinea candidiasis among others, are examples of onychomycosis and fungal infection.
  • Each are caused by different types of fungus such as those of the gena Trichophyton, Epidermophytia, Microsporum and Candida.
  • the present invention also relates to the use of the non-aqueous topical compositions for treating herpes infections.
  • Fungal infection of the nails is one of the most common diseases of the nail bed or plate. It is estimated that between 6 and 8 percent of the adult population is affected by such fungal infections to a varying degree. Fungal infections of the nail (onychomycosis) are often caused by dermatophytic fungi, most often by one of Trichophyton mentagrophytes (also known as Trichophyton interdigitale) and Trichophyton rubrum, although numerous other fungi are also known to cause such infections. Fungal infection of the skin such as Tinea pedis (athlete's foot), Tinea cruris (jock itch) and Tinea corporis are also commonly caused by T. rubrum and T. mentagrophytes, among other fungi. T.
  • Herpes is an infection that is caused by a herpes simplex virus. Oral herpes causes cold sores around the mouth and face. Genital herpes affects the genitals, buttocks or anal area. Herpes has no cure and can only be controlled by powerful anti-viral drugs.
  • compositions for use in the topical treatment of skin and nail fungal infections have been described in the art. These topical applications include lotions, sprays, gels, ointments and powders containing a variety of prescription and non-prescription active ingredients.
  • United States Patent 6,080,744 describes cream-based topical treatments for mycotic infections consisting of a blend containing multiple active ingredients including ketaconazole, nystatin, miconazole nitrate, tolnaftate, clotrimazole, undecenoic acid, zinc undecenoate, propionic acid and sodium propionate.
  • the compositions may include additional active ingredients such as an antibacterial agent ⁇ e.g. , gentamicin) or an anti-inflammatory agent (e.g. , dipropionate betamethasone).
  • an antibacterial agent e.g. gentamicin
  • an anti-inflammatory agent e.g. , dipropionate betamethasone
  • United States Patent 6,664,292 describes compositions for the treatment of fungal infections of the nail comprised of a lower alcohol, preferably methanol, and a single, lower carboxylic acid.
  • the composition is extremely volatile, however, and requires special storage considerations in order to prevent the methanol from evaporating.
  • United States Patent 4,824,865 describes compositions containing 2-hydroxyoctanoic acid, 2-ketooctanoic acid and C 2 to Ce esters thereof in aqueous and non-aqueous formulations for the treatment of various skin infections. There is no discussion of nail infections and the acidic pH of the water-containing formulations would result in irritation to the user.
  • United States Patent 6,214,889 describes liquid and gel compositions for the treatment of adverse skin conditions consisting of one or more of potassium, sodium, calcium or cesium formate alone or in combination, preferably in concentrations of about 50% in distilled water and an optional gelling agent.
  • the composition of this invention contains a very large amount of water and there is no teaching that it would be effective against nail infections.
  • United States Patent 6,921 ,529 describes a topical composition containing a weak organic acid dispersed in a non-biodegradeable polymeric matrix to form a supersaturated hydrogel.
  • the polymer is preferably a polyacrylate and the weak organic acid is acetic or citric acid.
  • the use of other, known, antimycotic agents such as azole derivatives, undecylenic acid, tea tree oil ⁇ Melaleuca alternifolia), or salicyclic acid may be added to the hydrogel.
  • a hydrogel contains a large amount of water and the use of these acids would result in an irritation to the end user
  • Nettleship discusses the use of a propionic acid-propionate-caprylate mixture in ointment or powder form to treat skin infections.
  • Peck and Russ (Archives of Dermatology and Syphilology, 1947, 56(5), 601) discuss the use of an aqueous ointment containing 12.3% sodium propionate, 2.7% propionic acid and 10% sodium caprylate to treat tinea infections of the scalp, rectum, nails and hands and feet. Treatment of the nails was cumbersome and arduous, requiring grinding of the nails until pain was induced, application of the ointment and alternating filing of the nails and application of the ointment twice a day for several months.
  • Mori et al (Agricultural and Biological Chemistry, 1987, 51 (12) 3403) examined the activity of various saturated and unsaturated fatty acids against Pyricularia oryzae and Miscanthus sinensis and concluded C 10 to C 13 monocarboxylic fatty acids were the most active. However, there is no discussion of clinical treatment of skin and nail infections. Kabara et al (Antimicrobial Agents and Chemotherapy, 1972, 2(1 ), 23) evaluated the activity in vitro of 15 saturated and unsaturated fatty acids against gram positive and gram negative bacteria. Thus (Ci 2 ) acid was found to be the most effective. However, there was no discussion of clinical treatment of skin and nail infections.
  • Garg and Muller (Mycoses, 1993, 36, 51) examined the in vitro antifungal activity of saturated and unsaturated C 7 to Ci 8 fatty acids against Trichophyton and Microsporum species that cause fungal infection. C 7 to C saturated fatty acids were most active against fungi that cause skin infection. However, there was no discussion of clinical treatment of skin and nail infection.
  • compositions for the treatment of fungal infections most of these compositions have a high loading of active ingredient, cause undesirable side effects and require an invasive or long treatment regimen.
  • the present invention relates to a non-toxic, topical antifungal composition for the treatment of fungal infections of the nails and skin.
  • the active ingredients of the antifungal composition comprise a combination of low molecular weight, hydrophilic carboxylic acid salts or derivatives exhibiting a synergistic enhancement, dissolved in a non-aqueous, non-volatile polyhydric carrier.
  • the composition can also contain a nail- penetrating agent to allow absorption of the composition into the nail. Since the source of onychomycosis can be traced to the nail bed, allowing the low molecular weight, hydrophilic carboxylic acid salts and/or derivatives to penetrate to the nail bed results in the most effective treatment of the fungal infection.
  • composition suitable for the topical treatment of a variety of fungal infections that may develop on the skin and nails comprising a combination of low molecular weight, hydrophilic organic acid salts or derivatives exhibiting a synergistic enhancement, dissolved in a non-aqueous, nonvolatile polyhydric carrier.
  • composition comprising a combination of low molecular weight, hydrophilic organic acid salts or derivatives exhibiting a synergistic enhancement and a penetrating agent, dissolved in a nonaqueous, non-volatile polyhydric carrier used to treat onychomycosis.
  • composition comprising a combination of low molecular weight organic acid salts or derivatives exhibiting a synergistic enhancement and a penetrating agent, dissolved in a non-aqueous, nonvolatile polyhydric carrier used to treat fungal infection.
  • a method of treatment using a composition comprising a combination of low molecular weight, hydrophilic carboxylic acid salts or derivatives exhibiting a synergistic enhancement and a penetrating agent, dissolved in a non-aqueous, non-volatile polyhydric solvent.
  • composition having an increased drug flux comprising a supersaturated concentration of low molecular weight, hydrophilic organic acid salts or derivatives.
  • the invention is suitable for use for the treatment of genital herpes and particularly herpes cold sores MORE DETAILED DESCRIPTION OF ASPECTS OF THE INVENTION
  • a non-toxic, topical antifungal composition comprising a combination of at least three or more low molecular weight, hydrophilic organic acid salts or derivatives exhibiting a still greater synergistic enhancement, dissolved in a carrier, wherein the low molecular weight organic acid salts are selected from the group consisting of saturated and unsaturated, acyclic, branched and unbranched aliphatic carboxylic acids wherein the longest carbon chain has eight carbons, and aromatic carboxylic acids containing less than ten carbon atoms; the carrier is comprised of one or more non-aqueous, non-volatile polyhydric solvents; and wherein the combination of low molecular weight, hydrophilic organic acid salts and/or derivatives comprises between about 0.5% to about 50%, preferably to about 30% and most preferably to about 10% by weight of the composition, and no single acid salt or derivative comprises more than about 75% by weight of the total acid content.
  • the active ingredients of the present antifungal compositions are combinations of at least three or more low molecular weight, hydrophilic organic acid salts or derivatives.
  • These low molecular weight, hydrophilic organic acids include both substituted and non-substituted aliphatic (saturated and unsaturated) and aromatic acids.
  • the carboxylic acid has less than 12, and more preferably less than ten carbons, with the longest carbon chain being eight carbon atoms in length and the aromatic carboxylic acid containing less than ten carbon atoms.
  • the carboxylic acids used in the present invention can be substituted by one or more functional groups, such as alkyl, alkenyl, alkynyl, halogen, hydroxy, carbonyl, carboxylic acid, aldehyde, ester, amide, carbonate, carbamate, ether, amino, cyano, isocyano, oxy, oxo, thia, aza, azide, imine, nitro, nitrate, nitroso, nitrosooxy, cyanate, isocyanate, thiocyanate, isothiocyanate, sulfinyl, sulfhydryl, sulfonyl, phosphino.
  • Each of the alkyl, alkenyl, alkynyl and amino groups may themselves be optionally substituted with one or more of the preceding functional groups.
  • the carboxylic acids are selected from branched and unbranched alkanoic acids, hydroxyalkanoic acids, alkenoic acid, aromatic acids, and hydroxyaromatic acids.
  • organic acids include formic, acetic, propionic, butyric, valeric, caproic, enanthic, caprylic, lactic, tartaric, gluconic, benzoic, mandelic, salicylic, acrylic, acetoacetic, pyruvic, adipic, aldaric, fumaric, glutaric, maleic, sorbic, malic, malonic, oxalic, succinic, tartronic, citric, isocitric, aconitic, and carballylic acids, as well as their further branched and substituted derivatives.
  • the salts of the carboxylic acids most useful in the present invention are preferably metal salts. More preferably, the metal salts are selected from the usual groups 1 and 2 metals and zinc. Groups 1 and 2 metal salts normally comprise lithium, sodium potassium, magnesium and calcium salts. Most preferably the metal salts used in the present invention are sodium, calcium and zinc. Most preferred active ingredients for the composition of the present invention are sodium acetate, sodium formate, zinc propionate, calcium propionate and sodium benzoate, and various combinations thereof. These compounds and other salts and/or derivatives can be grouped together in various amounts and in various numbers and provides substantially the same benefits, and groups of three, four or five salts and/or derivatives may be chosen to achieve the benefits of the invention.
  • Non-aqueous in this case means low to negligible water content, i.e. 5% and more preferably less than about 1 % water as formulated based on the weight of the composition.
  • the solvents used for the present compositions will preferably have a low to negligible water content.
  • the low molecular weight, hydrophilic carboxylic acid salts or derivatives of the present compositions are dissolved in a non-aqueous, non-volatile polyhydric solvent.
  • Polyhydric in this case means containing more than one hydroxyl group.
  • the solvents include glycerine, diglycerol, ethylene glycol, propylene glycol, low molecular weight polyglycols, such as polyethylene glycol or polypropylene glycol with molecular weight less than 500 gmol "1 , among others, and their derivatives, particularly monoether and ester derivatives. More preferred as solvents are glycerine and propylene glycol. Most preferred as a solvent is propylene glycol.
  • compositions of the present invention can also comprise from between about 1 % to about 80% preferably between about 30% and about 80%, more preferably between about 50% to about 70% of a penetrating agent to allow the low molecular weight, hydrophilic carboxylic acid salts or derivatives to penetrate the nail itself to ensure the carboxylic acid salts or derivatives contact the source of the fungal infection, usually the nail bed.
  • the penetrating agent may be selected from alcohols, preferably lower alkanols. More preferred alkanols are methanol, ethanol, n-propanol, isopropanol, n- butanol, sec-butanol and tert-butanol. Most preferred are isopropanol and ethanol.
  • An optional gel-forming component may be incorporated in the compositions of the invention to produce a formulation suitable for application to bandages, dressings and the like.
  • Preferred gel-forming ingredients are hydroxyl ethyl cellulose or a fumed silica (Aerosil®) which may be used in non-aqueous solvents or carriers.
  • compositions of the present invention comprise the combination of sodium acetate, sodium formate, zinc propionate, calcium propionate, and sodium benzoate or the above without sodium acetate in the non-aqueous, non-volatile polyhydric carrier propylene glycol, to which is added the penetrating agent ethanol or isopropanol.
  • Glycerol may optionally be added to alter the viscosity of the compositions of the present invention.
  • the combination of low molecular weight, hydrophilic carboxylic acid salts and/or derivatives in the present compositions may be added to the carrier at a level between about 1 % to about 50% total carboxylic acid salt or derivative content by weight of the composition.
  • the total combination of carboxylic acid salts or derivatives is between about 1 % to about 30% by weight of the composition, and more preferably the total synergistic combination of carboxylic acid salts or derivatives is between about 1 % to about 20% by weight of the composition.
  • the distribution of the individual carboxylic acid salts or derivatives within the total combination of carboxylic acid salts or derivatives is not limited, however. It is preferable that any one carboxylic acid salt or derivative does not comprise more than about 75% of the combination.
  • the individual carboxylic acid salts and/or derivatives are added to the carrier at a level of between about 1 % to about 10% by weight of the total formulation.
  • compositions of the present invention exhibit antifungal properties and are therefore useful in the topical treatment against fungi which cause onychomycosis and fungal infection such as tinea unguium, tinea pedis, tinea cruris, tinea corporis, tinea versicolor and tinea candidiasis.
  • the fungi causing these tinea infections include the various species of Trichophyton, Epidermophyton, Microsporum and Candida.
  • the compositions of the present invention are particularly useful in treating onychomycoses caused by T. mentagrophytes (also known as T. interdigitale) and T. rubrum, in particular 7. rubrum.
  • compositions of the invention can also be pre-applied to bandages or other absorbent material, which is then applied to the infected area.
  • the treated area can be wrapped in a bandage or other protective covering.
  • compositions described herein as a medicament is provided for the topical treatment of cold sores, in one embodiment herpes cold sores.
  • methods of treatment of onychomycosis and fungal infection have been provided wherein an effective amount of the compositions described herein is liberally applied to the infected area by applying by hand or painting.
  • topical treatment of fungal infection may include, but not be limited to, application of a gel formulation of the compositions of the present invention to the skin with repeated, daily application of the gel formulation until eradication of the fungal infection is achieved, for example singularly or repeatedly.
  • Topical treatment of onychomycosis may include, but not be limited to, painting the infected nail or nails with a liquid formulation of the compositions of the present invention with repeated, daily application of the liquid formulation until eradication of the fungal infection is achieved, for example singularly or repeatedly.
  • a bandage or dressing impregnated with a composition of the present invention further can be applied to maintain a steady level of the antifungal composition at the treatment site.
  • Other formulations of the compositions of the present invention that may be used to treat fungal infections of the skin and nails may include creams, lotions, ointments and the like.
  • compositions described herein in the preparation of a medicament for the topical treatment of onychomycosis and fungal infection is also provided.
  • compositions of the invention in the preparation of a medicament for the topical treatment of Candida infections is also provided.
  • Exemplary Formulations of the Herpes/Antifungal Compositions of the Invention may be prepared by the methods known to the skilled person. Two exemplary, but non-limiting, formulations of the present invention, a liquid and a gel formulation, are provided below. In addition to these exemplary formulations, other topical formulations, prepared using methods known to the skilled person, may also be used for the administration of the antifungal compositions of the present invention.
  • a preferred liquid formulation having low to negligible water content contains the following ingredients:
  • This formulation may be prepared by, among other methods, first warming the propylene glycol and sequentially dissolving in it, the sodium benzoate, calcium propionate, zinc propionate and sodium formate. After dissolution of each of the salts, the glycerol is added, following which the mixture is cooled to room temperature.
  • a preferred gel formulation having low to negligible water content contains the following ingredients:
  • Hydroxy ethyl cellulose 2 This formulation may be prepared by, among other methods, first warming the propylene glycol and sequentially dissolving in it the sodium benzoate, calcium propionate, zinc propionate and sodium formate. After dissolution of each of the salts, the hydroxy ethyl cellulose is slowly added to prevent agglomeration, following which the mixture is cooled to room temperature.
  • the antifungal activity of the present compositions was confirmed through in vitro testing using an antifungal microdilution method using Canadian Laboratory Standards Institute (CLSI) Reference Method 38-A2 with modifications as described below.
  • CLSI Canadian Laboratory Standards Institute
  • This method is the gold standard used in measuring the antifungal susceptibility of filamentous fungi that cause invasive infections.
  • Fungal colonies are grown on potato glucose agar (PGA).
  • PGA potato glucose agar
  • SGB Sabouraud glucose broth
  • Microdilution trays are incubated at 24 °C, and are read after 5 days of culture. Turbidity in the microdilution wells is scored with the aid of a reading mirror and compared with that of the growth control.
  • the turbidity scores (average of 3 tests) for T. rubrum and T. mentragrophytes grown in different concentrations (or dilutions) of test compounds for 5 days was as follows:
  • compositions of the current invention contain several carboxylic acid salts as the active ingredients.
  • the preferred carboxylic acid salts of the present invention have antifungal activity against T. mentogrophytes and T. rubrum.
  • the resultant antifungal activity is synergistic.
  • synergistic is defined to mean more than additive.
  • Example 5 Demonstration of Synergistic Activity: Addition of Zinc Propionate to a Mixture of Calcium Propionate, Sodium Benzoate and Sodium Formate
  • Example 7 Demonstration of Synergistic Activity: Addition of Sodium Acetate to the Liquid Formulation of Example 1 without Sodium Formate
  • Example 3 Using the broth assay of Example 3 the liquid formulation of Example 1 was tested against Candida albacans, Candida parapsilosis and Candida krusei. Against C.
  • Example 1 albicans an MIC value of 0.63% of the liquid formulation of Example 1 was determined. Against C. parapsilosis an MIC value of 0.63% of the liquid formulation of Example 1 was determined. Against C. krusei an MIC value of 0.31 % of the liquid formulation of Example 1 was determined.
  • Example 9 Penetrating Agent Action To the liquid formulation of Example 1 was added isopropanol or ethanol so that it comprised 25, 33, 50, 66, 75 or 80% of the weight of the formulation. The new formulations were applied to a human nail. The liquid formulation dried on the nail leaving no powdery residue indicating that the carboxylic acid salts were rapidly absorbed by the human nail.
  • Example 10 Treatment of Onychomycosis and Fungal infection
  • Example 1 In two individuals, each with fungal infections of the nail on all nails of both feet, the nails were first debrided to remove damaged nail material only. Following debridement, the liquid formulation of Example 1 was applied to each nail and the surrounding skin twice daily (morning and evening). Within two weeks, both individuals perceived a marked reduction in the sensation of irritation at the nails. Treatment was continued for eight weeks at which time cultures taken from one individual tested negative for nail fungus. Following cessation of treatment, reoccurrence of the infection was not reported by either individual. No irritation or other discomfort owing to the application of a composition of the invention was reported by either subject.
  • Example 1 In two individuals, each with a fungal infection of the nail on a big toe, the liquid formulation of Example 1 was applied twice daily (morning and evening) for eight weeks at which time there was no evidence of infection. Prior to treatment the nails were not debrided. Following cessation of treatment, reoccurrence of the infection was not reported by either individual. No irritation or other discomfort owing to the application of a composition of the invention was reported by either subject.
  • Example 2 One individual reported suffering from a fungal infection of the skin on the top and underside of the foot and between the toes.
  • the gel formulation of Example 2 was applied twice daily to this area. Although treatment was continued for eight weeks, the subject reported that the redness and irritation had cleared within two days
  • Example 1 One individual with fungal infections on the under arms and the back sides of the elbows was treated with the liquid formulation of Example 1 twice daily (morning and evening) for five days. Following cessation of treatment, both infections had been completely eradicated; no reoccurrence was reported. No irritation or other discomfort owing to the application of a composition of the invention was reported.
  • a synergistic enhancement by the low molecular weight, hydrophilic carboxylic acid salts or derivatives was observed in the treatment of fungal infections of the skin.
  • An aqueous solution of calcium and sodium propionate led to an initial clearing of fungal infections of the skin, however, the infections reoccurred within two weeks following cessation of treatment.
  • the infections were eradicated when using a composition of the present invention containing propionic acid and benzoic acid salts in propylene glycol, with an even greater synergistic enhancement observed through the addition of a third organic acid.

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Abstract

La présente invention concerne une composition antifongique locale toxique et l'utilisation de la composition dans le traitement des infections, ladite composition comprenant une combinaison d'au moins trois sels d'acide organique hydrophiles de faible masse molaire ou plus et/ou leurs dérivés présentant un effet synergique, dissous dans un vecteur, les sels d'acide organique de faible masse molaire étant choisis dans le groupe constitué par les acides carboxyliques aliphatiques saturés et insaturés, acycliques, ramifiés et non ramifiés, la plus longue chaîne carbonée comportant huit atomes de carbone, et les acides carboxyliques aromatiques comportant moins de dix atomes de carbone ; le vecteur comprenant un ou plusieurs solvants polyols non aqueux et non volatils ; et la combinaison de sels d'acide organique hydrophiles de faible masse molaire ou de leurs dérivés constitue entre environ 0,5 % et environ 50 % en masse de la composition, et aucun sel d'acide ou dérivé ne constitue plus d'environ 75 % en masse de la teneur totale en acides.
PCT/CA2010/001812 2009-05-15 2010-11-12 Compositions de sels d'acide organique pour administration locale adaptées au traitement des infections WO2012061920A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA2834381A CA2834381A1 (fr) 2010-11-12 2010-11-12 Compositions de sels d'acide organique pour administration locale adaptees au traitement des infections
US13/884,927 US20140142177A1 (en) 2009-05-15 2010-11-12 Topical organic acid salt compositions suitable for treating infections
PCT/CA2010/001812 WO2012061920A1 (fr) 2010-11-12 2010-11-12 Compositions de sels d'acide organique pour administration locale adaptées au traitement des infections
EP10859588.5A EP2637654A4 (fr) 2010-11-12 2010-11-12 Compositions de sels d'acide organique pour administration locale adaptées au traitement des infections

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WO2017029183A1 (fr) * 2015-08-18 2017-02-23 Bode Chemie Gmbh Agent désinfectant contenant des acides organiques

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US4197316A (en) * 1975-07-23 1980-04-08 Scott Eugene J Van Treatment of dry skin
US4849221A (en) * 1985-12-12 1989-07-18 Bernd Marquardt Pharmaceutical product, containing a mixture of benzoic acid, phenol and an alkali fluoride, for the topical treatment of herpes virus efflorescences, and method for treatment of herpes simplex efflorescences in the human
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EP2637654A4 (fr) 2014-05-28
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