WO1988006884A1 - A pharmaceutical composition used for the topical treatment of nail mycosis and a process for preparing same - Google Patents

A pharmaceutical composition used for the topical treatment of nail mycosis and a process for preparing same Download PDF

Info

Publication number
WO1988006884A1
WO1988006884A1 PCT/HU1988/000012 HU8800012W WO8806884A1 WO 1988006884 A1 WO1988006884 A1 WO 1988006884A1 HU 8800012 W HU8800012 W HU 8800012W WO 8806884 A1 WO8806884 A1 WO 8806884A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
topical
imidazole
ester
antimycotic
Prior art date
Application number
PCT/HU1988/000012
Other languages
French (fr)
Inventor
Gyöngyi LENGYELNÉ HORVÁTH
Jeno^" NÉMETH
Original Assignee
Lengyelne Horvath Gyoengyi
Nemeth Jenoe
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 Lengyelne Horvath Gyoengyi, Nemeth Jenoe filed Critical Lengyelne Horvath Gyoengyi
Publication of WO1988006884A1 publication Critical patent/WO1988006884A1/en

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • 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
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4946—Imidazoles or their condensed derivatives, e.g. benzimidazoles
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q3/00—Manicure or pedicure preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q3/00—Manicure or pedicure preparations
    • A61Q3/02—Nail coatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures

Definitions

  • the invention relates to a pharmaceutical composition suitable for the topical treatment of nail mycosis and a process for preparing the composition.
  • Nail mycosis (onychomycosis) is a very frequent disease the treatment of which is very difficult. This disease is medicated by systemic treatment, by the oral addition of antimycotics, in this case, however, a highly increased therapeutical dose should be administered into the organism, as a consequence of which the organism suffers injuries by strong side-effects.
  • the topical treatment is carried out by using paintings and ointments. The disadvantage of these paintings and ointments is that they do not remain long-lasting on the nail surface, this treatment requires therefore the use of occlusive bandage, which hinders the patient in using his treated limb.
  • a further disadvantage of the known topical treatment is that it is only rarely successful.
  • the most radical method of treatment of nail mycosis is the ablation (surgical removal) of the nail which is, however, on one hand a very painful intervention, on the other hand, the patient. is unable to. work for a long time.
  • Aim of the invention is to prepare a composition enabling the topical treatment of nail mycosis.
  • the composition according to the invention assures a long-lasting active ingredient concentration, it cannot be washed with water and can be used very easily and the patient is not hindered in working during the therapy.
  • composition comprising a pharmaceutically effective amount of a topical antimycotic, preferably that of imidazole structure and optionally of an antiseptic, preferably salicylic acid or a salt or ester thereof dissolved if necessary in an organic solvent, preferably in a lower alcohol or in the ester thereof formed with lower carboxylic acid, a coat forming agent preferably colloidion and optionally a lower polyvalent alcohol.
  • a topical antimycotic preferably that of imidazole structure and optionally of an antiseptic, preferably salicylic acid or a salt or ester thereof dissolved if necessary in an organic solvent, preferably in a lower alcohol or in the ester thereof formed with lower carboxylic acid, a coat forming agent preferably colloidion and optionally a lower polyvalent alcohol.
  • antimycotics especially compounds of imidazole structure usable for topical treatment remain effective for a long time, if they are admixed to coat forming agents - if necessary with suitable additives and in solvents, resp. - and applied onto the surface to be treated in the form of nail polish.
  • composition for treating nail mycosis is prepared according to the invention in a way that a topical antimycotic active ingredient, preferably an antimycotic of imidazole structure and optionally an antiseptic compound, preferably salicylic acid or the salt or ester thereof is formed into nail polish by dissolving them if necessary in an organic solvent, preferably in lower alcohol or in the ester thereof formed with a lower carboxylic acid, and by mixing them with a coat forming agent, preferably with collodion as well as optionally with a lower polyvalent alcohol.
  • a topical antimycotic active ingredient preferably an antimycotic of imidazole structure and optionally an antiseptic compound, preferably salicylic acid or the salt or ester thereof is formed into nail polish by dissolving them if necessary in an organic solvent, preferably in lower alcohol or in the ester thereof formed with a lower carboxylic acid, and by mixing them with a coat forming agent, preferably with collodion as well as optionally with a lower polyvalent
  • topical antimycotic active ingredient preferably 1-(2-chlorophenyl- ⁇ , ⁇ -diphenylbenzyl)-imidazole or 1-(2,4-dichloro- ⁇ -/2,4-dichlorobenzyloxy/-phenetyl)imidazole is used.
  • compounds of antimycotic activity known per se can also be used, but owing to the wide spectrum as well as the long duration of effect the mentioned compounds proved to be the most preferable concerning the invention.
  • an antiseptic compound could optionally be used for preparing the composition in order to prolong the effect of the antimycotics.
  • Salicylic acid or a salt of ester thereof are preferably used utilizing the keratolytic activity of these compounds.
  • a coat forming agent preferably collodion, i.e. an about 4 % solution of nitrocellulose in ether-alcohol micture of 3 : 1 ratio of volume is used. After the solvent is evaporated this material forms a long-lasting waterproof coating on the surface to be treated and assures at the same time that the active ingredient remains stable and acts with suitable intensity.
  • the thus-formed lacquer coat can further be improved, namely its elasticity can be increased (its cracking can be prevented) and the effectivity of the active ingredient therein can be enhanced if a lower polyvalent alcohol, preferably propylene glycol is added to the composition as further carrier.
  • a lower polyvalent alcohol preferably propylene glycol
  • the amount of the ingredients of the composition is determined by the circumstances of the preparation and storage of said nail polish as well as circumstances of use.
  • the composition contains besides 1 part by weight of antimycotic 2-5 parts by weight of antiseptic, and an organic solvent, if needed, in an amount up to 40 parts by weight, preferably 5-35 parts by weight, 15-35 parts by weight of a coat forming agent and, if needed, 3-15 parts by weight of a lower polyvalent alcohol.
  • the composition is prepared by the simple mixing of the components.
  • the active ingredients are admixed to the other ingredients of the composition in themselves or if they are hardly soluble in the carriers, then dissolved in an organic solvent, preferably in a lower alcohol or ester, e.g. absolute ethyl alcohol or ethyl acetate.
  • composition obtained by the mixing of the active ingredients and carriers can effectively be used for treating nail mycosis caused by a wide variety of fungus strains.
  • the composition can be used especially against infections caused by Trychophyton species but it is also effective against Candida albicans, Scopulariopsis brevtcaulis and other fungus strains.
  • the composition can be used in the human and veterinary therapy, as well. In latter case it may be used for treating onychomycosis of meat-eating animals. It is particularly useful for treating dogs and cats but it can be applied to any other meat-eating animals, too.
  • the treatment is very simple and easy, the composition is applied onto the nail and the thusformed lacquer coat is renewed from time to time.
  • the nail mycosis can be alleviated by a regular treatment for 1 to 6 month. Further one month treatment is advisable after the alleviation of the symptoms in order to prevent the renewed infection.
  • composition of the invention enables the treatment of nail mycosis involving no painful intervention or deleterious side effects to the organism.
  • the application of the composition is simple and makes the treatment of nail mycosis much easier.
  • Example 1 The invention is described more detailed in the following Examples. In the Examples “part” means part by weight. Example 1
  • a composition is prepared against nail mycosis with the following composition:
  • a composition is prepared against nail mycosis containing the following compounds: 0.4 part of 1-/2,4-dichloro- ⁇ -(2,4-dichlorobenzyloxy)-phenethyl)-imidazole antimycotic, 1.0 part of salicylic acid antiseptic, 4.0 part of ethylacetate solvent, 4.0 part of propylene glycol carrier additive,
  • composition is prepared from the active ingredients and the other components according to Example 1.
  • composition of the invention The stability and biological activity of the composition of the invention have been examined in vitro,while their therapeutical usability has been tested in vivo. The details of the examination are described as follows.
  • compositions according to Examples 1 and 2 as well as those having similar composition but containing no salicylic acid have been examined in vitro.
  • the tests were carried out according to the prescriptions of the Országos Gydgyszerészeti Inté- zet (Hungarian Pharmaceutical Institute).
  • the test compositions have been kept on room temperature for six months and they have been examined from time to time for strange organic materials and decomposition products.
  • compositions containing the active ingredient according to Example 1 From the compositions containing the active ingredient according to Example 1 a sample was taken corresponding to 500 ⁇ g. of antimycotic, from which a thin layer chromatogram was made in contrast to the pure active ingredient with a 4:6 ratio of volume chloroformmethanol mixture; the chromatogram was made visible with the glacial acetic acidic-aqueous solution of potassium iodide. No imidazole decomposition product was detected even after six months. For examining carbinol decomposition products a thin layer chromatogram was made from samples similar as described before, developed this time with saturated diisopropvlether. The chromatogram was evaluated in ultraviolet light. No decomposition product could be detected either, even after six months.
  • compositions containing the active ingredient according to Example 2 From the compositions containing the active ingredient according to Example 2 a sample was taken corresponding to 200 ⁇ g. of antimycotics. A thin layer chromatogram was developed with a 6:3:1 ratio of volume n-hexane-chloroform-methanol mixture and evaluated as described before in iodine vapour atmosphere. It was found that the composition contained no strange organic materials indetectable amount even after a storage for six months.
  • compositions were examined according to the disc method specified in 6th Eddition of Pharmacopea Hungarica for the biological evaluation of antibiotics, by using self-prepared test discs.
  • the samples of the composition according to Examples 1 and 2 prepared by chain dilution according to the prescription were applied to the culture of test fungus strains inoculated into culture medium and the extinction ring was examined by different concentrations.
  • the examinations were carried out on Candida alblcans, Scopulariopsis brevicaulis as well as on Trichophyton rubrum and Menthagrophytes strains, respectively.
  • compositions according to Examples 1 and 2 proved to be the most effective against the Trichophyton strains, they showed an intensive activity against the Candida albicans strain and showed a good result against the Scopulariopsis brevicaulis strains, too. This result is very interesting considering the Trichophyton strains are fast always present among the pathogens of nail mycosis, without their killing the nail mycosis cannot be alleviated.
  • the therapeutical examination was carried out on groups of 58 voluntary patients. The patient suffering from nail mycosis have been instructed to treat their nails with the composition of Example 1 keeping the lacquer coat constantly. The patients have been examined after 28 weeks, then after further 6 weeks and the results were evaluated using the following scale:
  • the following Table shows the percentage ratio of the patients having reached the different recovery levels at the end of the examination period.

Abstract

The invention relates to a pharmaceutical composition usable for the topical treatment of nail mycosis and a process for the preparation of the composition. The composition of the invention comprises a pharmaceutically effective amount of a topical antimycotic, preferably that of imidazole structure and optionaly of an antiseptic, preferably salicylic acid or a salt or ester thereof dissolved if necessary in an organic solvent, preferably in a lower alcohol or in the ester thereof formed with lower carboxylic acid, a coat forming agent, preferably collodion and optionally a lower polyvalent alcohol. The composition is prepared by mixing the ingredients. The composition can simply and easily be used and enables the treatment of nail mycosis without any painful intervention or deleterious side effects to the organism.

Description

A PHARMACEUTICAL COMPOSITION USED FOR THE TOPICAL TREATMENT OF NAIL MYCOSIS AND A PROCESS FOR PREPARING SAME
The invention relates to a pharmaceutical composition suitable for the topical treatment of nail mycosis and a process for preparing the composition. Nail mycosis (onychomycosis) is a very frequent disease the treatment of which is very difficult. This disease is medicated by systemic treatment, by the oral addition of antimycotics, in this case, however, a highly increased therapeutical dose should be administered into the organism, as a consequence of which the organism suffers injuries by strong side-effects. According to another method the topical treatment is carried out by using paintings and ointments. The disadvantage of these paintings and ointments is that they do not remain long-lasting on the nail surface, this treatment requires therefore the use of occlusive bandage, which hinders the patient in using his treated limb. A further disadvantage of the known topical treatment is that it is only rarely successful. The most radical method of treatment of nail mycosis is the ablation (surgical removal) of the nail which is, however, on one hand a very painful intervention, on the other hand, the patient. is unable to. work for a long time.
So there is a need of a much simpler therapy of nail mycosis, which has less side effects to the organism.
Aim of the invention is to prepare a composition enabling the topical treatment of nail mycosis. The composition according to the invention assures a long-lasting active ingredient concentration, it cannot be washed with water and can be used very easily and the patient is not hindered in working during the therapy.
It has been found that the above aim can be achieved by a composition comprising a pharmaceutically effective amount of a topical antimycotic, preferably that of imidazole structure and optionally of an antiseptic, preferably salicylic acid or a salt or ester thereof dissolved if necessary in an organic solvent, preferably in a lower alcohol or in the ester thereof formed with lower carboxylic acid, a coat forming agent preferably colloidion and optionally a lower polyvalent alcohol.
The basis of the invention is the recognition that antimycotics, especially compounds of imidazole structure usable for topical treatment remain effective for a long time, if they are admixed to coat forming agents - if necessary with suitable additives and in solvents, resp. - and applied onto the surface to be treated in the form of nail polish.
On the basis of the above recognition a composition for treating nail mycosis is prepared according to the invention in a way that a topical antimycotic active ingredient, preferably an antimycotic of imidazole structure and optionally an antiseptic compound, preferably salicylic acid or the salt or ester thereof is formed into nail polish by dissolving them if necessary in an organic solvent, preferably in lower alcohol or in the ester thereof formed with a lower carboxylic acid, and by mixing them with a coat forming agent, preferably with collodion as well as optionally with a lower polyvalent alcohol. As topical antimycotic active ingredient preferably 1-(2-chlorophenyl-α,α-diphenylbenzyl)-imidazole or 1-(2,4-dichloro-β-/2,4-dichlorobenzyloxy/-phenetyl)imidazole is used. In addition to the above-mentioned compound of imidazole structure, however, compounds of antimycotic activity known per se can also be used, but owing to the wide spectrum as well as the long duration of effect the mentioned compounds proved to be the most preferable concerning the invention.
In addition to the compound of antimycotic activity an antiseptic compound could optionally be used for preparing the composition in order to prolong the effect of the antimycotics. Salicylic acid or a salt of ester thereof are preferably used utilizing the keratolytic activity of these compounds. As carrier of the composition a coat forming agent, preferably collodion, i.e. an about 4 % solution of nitrocellulose in ether-alcohol micture of 3 : 1 ratio of volume is used. After the solvent is evaporated this material forms a long-lasting waterproof coating on the surface to be treated and assures at the same time that the active ingredient remains stable and acts with suitable intensity. It has been found, however, that the thus-formed lacquer coat can further be improved, namely its elasticity can be increased (its cracking can be prevented) and the effectivity of the active ingredient therein can be enhanced if a lower polyvalent alcohol, preferably propylene glycol is added to the composition as further carrier.
The amount of the ingredients of the composition is determined by the circumstances of the preparation and storage of said nail polish as well as circumstances of use. Preferably, the composition contains besides 1 part by weight of antimycotic 2-5 parts by weight of antiseptic, and an organic solvent, if needed, in an amount up to 40 parts by weight, preferably 5-35 parts by weight, 15-35 parts by weight of a coat forming agent and, if needed, 3-15 parts by weight of a lower polyvalent alcohol.
The composition is prepared by the simple mixing of the components. The active ingredients are admixed to the other ingredients of the composition in themselves or if they are hardly soluble in the carriers, then dissolved in an organic solvent, preferably in a lower alcohol or ester, e.g. absolute ethyl alcohol or ethyl acetate.
The composition obtained by the mixing of the active ingredients and carriers can effectively be used for treating nail mycosis caused by a wide variety of fungus strains. The composition can be used especially against infections caused by Trychophyton species but it is also effective against Candida albicans, Scopulariopsis brevtcaulis and other fungus strains.
The composition can be used in the human and veterinary therapy, as well. In latter case it may be used for treating onychomycosis of meat-eating animals. It is particularly useful for treating dogs and cats but it can be applied to any other meat-eating animals, too.
The treatment is very simple and easy, the composition is applied onto the nail and the thusformed lacquer coat is renewed from time to time. Depending on the seriousness of the infection the nail mycosis can be alleviated by a regular treatment for 1 to 6 month. Further one month treatment is advisable after the alleviation of the symptoms in order to prevent the renewed infection.
Advantage of the invention is that the composition of the invention enables the treatment of nail mycosis involving no painful intervention or deleterious side effects to the organism. The application of the composition is simple and makes the treatment of nail mycosis much easier.
The invention is described more detailed in the following Examples. In the Examples "part" means part by weight. Example 1
A composition is prepared against nail mycosis with the following composition:
0.4 part of 1-/2-chlorophenyl-α,α-diphenylbenzyl/-imidazole antimycotics, 1.0 part of salicylic acid antiseptic, 8.0 part of absolute alcohol solvent,
2.0 part of propylenglycol carrier additive, 8.6 part of collodion carrier. The two active ingredients are dissolved in alcohol and the alcoholic solution is mixed with the mixture of propylenglycol and collodion. The lacquer thus-obtained is ready for use. Example 2
A composition is prepared against nail mycosis containing the following compounds: 0.4 part of 1-/2,4-dichloro-β-(2,4-dichlorobenzyloxy)-phenethyl)-imidazole antimycotic, 1.0 part of salicylic acid antiseptic, 4.0 part of ethylacetate solvent, 4.0 part of propylene glycol carrier additive,
10.6 part of collodion carrier. The composition is prepared from the active ingredients and the other components according to Example 1.
The stability and biological activity of the composition of the invention have been examined in vitro,while their therapeutical usability has been tested in vivo. The details of the examination are described as follows.
The stability of compositions according to Examples 1 and 2 as well as those having similar composition but containing no salicylic acid have been examined in vitro. The tests were carried out according to the prescriptions of the Országos Gydgyszerészeti Inté- zet (Hungarian Pharmaceutical Institute). The test compositions have been kept on room temperature for six months and they have been examined from time to time for strange organic materials and decomposition products.
From the compositions containing the active ingredient according to Example 1 a sample was taken corresponding to 500 μg. of antimycotic, from which a thin layer chromatogram was made in contrast to the pure active ingredient with a 4:6 ratio of volume chloroformmethanol mixture; the chromatogram was made visible with the glacial acetic acidic-aqueous solution of potassium iodide. No imidazole decomposition product was detected even after six months. For examining carbinol decomposition products a thin layer chromatogram was made from samples similar as described before, developed this time with saturated diisopropvlether. The chromatogram was evaluated in ultraviolet light. No decomposition product could be detected either, even after six months.
From the compositions containing the active ingredient according to Example 2 a sample was taken corresponding to 200 μg. of antimycotics. A thin layer chromatogram was developed with a 6:3:1 ratio of volume n-hexane-chloroform-methanol mixture and evaluated as described before in iodine vapour atmosphere. It was found that the composition contained no strange organic materials indetectable amount even after a storage for six months.
The biological effectivity of the compositions were examined according to the disc method specified in 6th Eddition of Pharmacopea Hungarica for the biological evaluation of antibiotics, by using self-prepared test discs. The samples of the composition according to Examples 1 and 2, prepared by chain dilution according to the prescription were applied to the culture of test fungus strains inoculated into culture medium and the extinction ring was examined by different concentrations. The examinations were carried out on Candida alblcans, Scopulariopsis brevicaulis as well as on Trichophyton rubrum and Menthagrophytes strains, respectively. The compositions according to Examples 1 and 2 proved to be the most effective against the Trichophyton strains, they showed an intensive activity against the Candida albicans strain and showed a good result against the Scopulariopsis brevicaulis strains, too. This result is very interesting considering the Trichophyton strains are fast always present among the pathogens of nail mycosis, without their killing the nail mycosis cannot be alleviated. The therapeutical examination was carried out on groups of 58 voluntary patients. The patient suffering from nail mycosis have been instructed to treat their nails with the composition of Example 1 keeping the lacquer coat constantly. The patients have been examined after 28 weeks, then after further 6 weeks and the results were evaluated using the following scale:
A. the position before treatment (100 % mycosis) B: uncertain decrease (recovery in a degree less than 25 %) C: the infected surface decreased by 25-50 % D: the infected surface decreased by 50-75 % E: the infected surface decreased in a degree greater than 75 % F: the nail is clinically free from symptoms. The following Table shows the percentage ratio of the patients having reached the different recovery levels at the end of the examination period.
Extent After a treatment After a treatment of recovery for 28 weeks for 34 weeks
B 10.4 % 8.6 %
C 11.5 % 7.5 %
D 20.5 % 32.5 %
E 30.6 % 9.4 %
F 27.0 % 42.0 % Though the examinations were not carried out under clinical conditions (neither the identification of the pathogenic fungus strains nor the control of the exact keeping of the treating instructions were examined) the results show that the composition of the invention can effectively be used for the medical treatment of nail mycosis.

Claims

1. Composition usable for the topical treatment of nail mycosis comprising a pharmaceutically effective amount of a topical antimycotic, preferably that of imidazole structure and optionally of an antiseptic, preferably salicylic acid or a salt or ester thereof dissolved if necessary in an organic solvent, preferably in a lower alcohol or in the ester thereof formed with lower carboxylic acid, a coat forming agent, preferably collodion and optionally a lower polyvalent alcohol.
2. A composition as claimed in claim 1 comprising 1-(2-chlorophenyl-α—α-diphenylbenzyl)-imidazole as topical antimycotic.
3. A composition as claimed in claim 1 comprising 1-/2,4-dichloro-β-(2,4-dichlorobenzyloxy)-phenethyl/-imidazole as topical antimycotic.
4. A composition as claimed in any of claims 1 to 3 comprising propylene glycol as lower polyvalent alcohol.
5. Process for preparing a composition used for the topical treatment of nail mycosis, c h a r a c t e r i z e d in that a topical antimycotic active ingredient, preferably an antimycotic of imidazole structure and optionally an antiseptic compound, preferably salicylic acid or the salt or ester thereof - dissolved if necessary in an organic solvent, preferably in a lower alcohol or in the ester thereof formed with lower carboxylic acid - is mixed with a coat forming agent, preferably with collodion, as well as optionally with a lower polyvalent alcohol and formed into nail polish.
6. A process according to claim 5, which comprises using 1-(2-chlorophenyl-α-α-diphenylbenzyl)-imidazole as topical antimycotic active ingredient.
7. A process according to claim 5, which comprises using 1-/2, 4-dichloro-β-(2,4-dichlorobenzyloxy)-phenethyl/-imidazole as topical antimycotic active ingredient.
8. A process according to any of claims 5 to 7 which comprises using propyleneglycol as lower polyvalent alcohol.
PCT/HU1988/000012 1987-03-09 1988-03-08 A pharmaceutical composition used for the topical treatment of nail mycosis and a process for preparing same WO1988006884A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
HU98787A HU200914B (en) 1987-03-09 1987-03-09 Process for producing new medical dosage unit suitable for local treatment of fungus infection of nails
HU987/87 1987-03-09

Publications (1)

Publication Number Publication Date
WO1988006884A1 true WO1988006884A1 (en) 1988-09-22

Family

ID=10952327

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/HU1988/000012 WO1988006884A1 (en) 1987-03-09 1988-03-08 A pharmaceutical composition used for the topical treatment of nail mycosis and a process for preparing same

Country Status (3)

Country Link
AU (1) AU1424988A (en)
HU (1) HU200914B (en)
WO (1) WO1988006884A1 (en)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0515312A2 (en) * 1991-05-23 1992-11-25 Sandoz Ltd. Pharmaceutical composition containing terbinafine as an anti-mycotic agent
WO1994008591A1 (en) * 1992-10-15 1994-04-28 Schering-Plough Healthcare Products, Inc. Treatment for onychomycosis topically applying salicylic acid, optionally in combination with a retinoid
WO1999049835A1 (en) * 1998-03-31 1999-10-07 Johnson And Johnson Consumer Companies, Inc. An acidified composition for topical treatment of nail and skin conditions
WO2003026710A1 (en) * 2001-09-26 2003-04-03 Mbs Multination Business Services (M.E.) Ltd. Mixture for use as a protective dressing
WO2003026709A1 (en) * 2001-09-26 2003-04-03 Mbs Multination Business Services (G.B.) Ltd. Liquid mixture for use as a dressing spray
US6596325B1 (en) * 1998-04-02 2003-07-22 Vroom Rene Werenfridus Lodewijk Composition for the treatment of hoof conditions in hoofed animals
US8193233B2 (en) 2009-02-13 2012-06-05 Topica Pharmaceuticals, Inc. Anti-fungal formulation
US8697753B1 (en) 2013-02-07 2014-04-15 Polichem Sa Method of treating onychomycosis
JP2015515960A (en) * 2012-05-02 2015-06-04 サード, サミーSAAD, Samy Topical non-aqueous pharmaceutical formulation
ES2556253R1 (en) * 2014-07-11 2016-02-02 R&D Pharma Antifungal preparations intended for local onychomycosis treatment

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2423849A1 (en) * 1973-05-17 1974-12-12 Minnesota Mining & Mfg FILM-FORMING PREPARATION FOR LOCAL SKIN USE
EP0054205A1 (en) * 1980-12-05 1982-06-23 Bayer Ag Anti-fungal composition in emulsion form with a higher release rate of the drug
EP0055397A1 (en) * 1980-12-05 1982-07-07 Bayer Ag Antifungal compositions with a high release rate of the drug as an elastic liquid dressing
EP0055396A1 (en) * 1980-12-05 1982-07-07 Bayer Ag Antifungal compositions with a high release rate of the drug as an elastic liquid dressing
EP0070525A2 (en) * 1981-07-22 1983-01-26 Toko Yakuhin Industry Co., Ltd. Fungicidal preparations for external use
EP0186055A2 (en) * 1984-12-25 1986-07-02 Bayer Ag Antimycotic gel preparations
WO1987002580A1 (en) * 1985-11-04 1987-05-07 Dermatological Products Of Texas Film-forming, pharmaceutical vehicles for application of medicaments to nails, pharmaceutical compositions based on those vehicles, and methods of using same
EP0226984A1 (en) * 1985-12-19 1987-07-01 Hoechst Aktiengesellschaft Antimycotic nail varnish

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2423849A1 (en) * 1973-05-17 1974-12-12 Minnesota Mining & Mfg FILM-FORMING PREPARATION FOR LOCAL SKIN USE
EP0054205A1 (en) * 1980-12-05 1982-06-23 Bayer Ag Anti-fungal composition in emulsion form with a higher release rate of the drug
EP0055397A1 (en) * 1980-12-05 1982-07-07 Bayer Ag Antifungal compositions with a high release rate of the drug as an elastic liquid dressing
EP0055396A1 (en) * 1980-12-05 1982-07-07 Bayer Ag Antifungal compositions with a high release rate of the drug as an elastic liquid dressing
EP0070525A2 (en) * 1981-07-22 1983-01-26 Toko Yakuhin Industry Co., Ltd. Fungicidal preparations for external use
EP0186055A2 (en) * 1984-12-25 1986-07-02 Bayer Ag Antimycotic gel preparations
WO1987002580A1 (en) * 1985-11-04 1987-05-07 Dermatological Products Of Texas Film-forming, pharmaceutical vehicles for application of medicaments to nails, pharmaceutical compositions based on those vehicles, and methods of using same
EP0226984A1 (en) * 1985-12-19 1987-07-01 Hoechst Aktiengesellschaft Antimycotic nail varnish

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
D. HANTSCHKE, "Mykosen", Volume 19, published 1976, Grosse Verlag (Berlin), J. VANDERDOUCKT et al., "Miconazole Alcoholic Solution in the Treatment of Mycotic Nail Infections", see pages 251-256, especially page 251. *
Die Pharmazie, Vol. 36, published 1981, Berlin, DDR, W. HORSCH et al., "Beitraege zur Arzneistoffliberation aus Suspensionssalben", see pages 24-28, especially page 25, table 1, preparation G. *
E. MUTSCHLER, "Arzneimittelwirkungen", fifth edition, published 1986, Wissenschaftliche Verlagsgesellschaft m.b.H. Stuttgart, see pages 621-624. *
PATENT ABSTRACTS OF JAPAN, unexamined applications, C Section, Volume 10, No. 98, Arpil 15, 1986 (15.04.86), The Patent Office Japanese Government, page 38 C 339; & JP,A,60 228 412 (TERUMO KK). *

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6319509B1 (en) 1991-05-23 2001-11-20 Novartis Ag Pharmaceutical composition
FR2676647A1 (en) * 1991-05-23 1992-11-27 Sandoz Sa NEW FORMULATIONS FOR LOCAL APPLICATION CONTAINING ALLYLAMINE AND THEIR USE.
EP0515312A3 (en) * 1991-05-23 1993-04-14 Sandoz Ltd. Pharmaceutical composition containing terbinafine as an anti-mycotic agent
US5866105A (en) * 1991-05-23 1999-02-02 Novartis Ag Pharmaceutical composition
US6214360B1 (en) 1991-05-23 2001-04-10 Novartis Ag Pharmaceutical composition
EP0515312A2 (en) * 1991-05-23 1992-11-25 Sandoz Ltd. Pharmaceutical composition containing terbinafine as an anti-mycotic agent
WO1994008591A1 (en) * 1992-10-15 1994-04-28 Schering-Plough Healthcare Products, Inc. Treatment for onychomycosis topically applying salicylic acid, optionally in combination with a retinoid
US5464610A (en) * 1992-10-15 1995-11-07 Schering-Plough Healthcare Products, Inc. Method for treating onychomycosis
US6416749B1 (en) 1992-10-15 2002-07-09 Schering-Plough Healthcare Products, Inc. Treatment for onychomycosis topically applying salicylic acid, optionally in combination with a retinoid
JP2002509867A (en) * 1998-03-31 2002-04-02 ジョンソン・アンド・ジョンソン・コンシューマー・カンパニーズ・インコーポレイテッド Acidified composition for topical treatment of nails and skin
US6231875B1 (en) 1998-03-31 2001-05-15 Johnson & Johnson Consumer Companies, Inc. Acidified composition for topical treatment of nail and skin conditions
WO1999049835A1 (en) * 1998-03-31 1999-10-07 Johnson And Johnson Consumer Companies, Inc. An acidified composition for topical treatment of nail and skin conditions
US6596325B1 (en) * 1998-04-02 2003-07-22 Vroom Rene Werenfridus Lodewijk Composition for the treatment of hoof conditions in hoofed animals
WO2003026710A1 (en) * 2001-09-26 2003-04-03 Mbs Multination Business Services (M.E.) Ltd. Mixture for use as a protective dressing
WO2003026709A1 (en) * 2001-09-26 2003-04-03 Mbs Multination Business Services (G.B.) Ltd. Liquid mixture for use as a dressing spray
US8193232B2 (en) 2009-02-13 2012-06-05 Topica Pharmaceuticals, Inc. Anti-fungal formulation
US8193233B2 (en) 2009-02-13 2012-06-05 Topica Pharmaceuticals, Inc. Anti-fungal formulation
US8362059B2 (en) 2009-02-13 2013-01-29 Topica Pharmaceuticals, Inc. Anti-fungal formulation
JP2015515960A (en) * 2012-05-02 2015-06-04 サード, サミーSAAD, Samy Topical non-aqueous pharmaceutical formulation
US8697753B1 (en) 2013-02-07 2014-04-15 Polichem Sa Method of treating onychomycosis
US9107877B2 (en) 2013-02-07 2015-08-18 Polichem Sa Method of treating onychomycosis
US10172811B2 (en) 2013-02-07 2019-01-08 Polichem Sa Topical antifungal composition for treating onychomycosis
ES2556253R1 (en) * 2014-07-11 2016-02-02 R&D Pharma Antifungal preparations intended for local onychomycosis treatment

Also Published As

Publication number Publication date
HUT46850A (en) 1988-12-28
HU200914B (en) 1990-09-28
AU1424988A (en) 1988-10-10

Similar Documents

Publication Publication Date Title
EP0247142B1 (en) Film-forming, pharmaceutical vehicles for application of medicaments to nails, pharmaceutical compositions based on those vehicles, and methods of using same
RU2088617C1 (en) Transdermal anhydrous composition, method of its preparing and application
JP3000104B2 (en) Compositions and methods for forming a film at native sites on body tissue
HUE020998T4 (en) Therapeutic compositions comprising ingenol-3-angelate
CH671157A5 (en) STABLE PHARMACEUTICAL PREPARATION CONTAINING GRANULOCYT COLONY STIMULATING FACTOR, AND METHOD FOR PRODUCING THE SAME.
CA2000837A1 (en) Gel bases for pharmaceutical compositions
JP2007534764A (en) Antifungal drug delivery
KR20120015319A (en) Compositions suitable for the topical treatment of fungal infections of the skin and nails
EP0137627B1 (en) Pour-on formulation for the control of parasites
JP3803393B2 (en) Nail ringworm treatment composition
WO1994015591A1 (en) Onychomycosis remedy composition
WO1988006884A1 (en) A pharmaceutical composition used for the topical treatment of nail mycosis and a process for preparing same
EP1059928A1 (en) Inorganic nitrite and organic acid in combination as topical antiviral composition
WO1996011710A1 (en) External preparation for nail ringworm
US20100272783A1 (en) Methods of Treating Infections of the Nail
RU2286764C1 (en) Agent of prolonged action for treatment of mouth cavity inflammation diseases
JP2020533417A (en) Antibacterial composition
FR2482860A1 (en) COMPOSITION AND PREPARATION OF AN ANTIMICROBIAL AGENT
US3932653A (en) Composition and method for topical administration of griseofulvin
EP0285856A2 (en) Use of dihydroergotamine and its salts in the local treatment of trophic disorders
EP0064830B1 (en) Pharmaceutical compositions for treating nail infections
JP2001501609A (en) Antifungal gel with high active compound release
JP2951725B2 (en) Topical composition for tinea unguium
EP0304374B1 (en) Therapeutical preparation containing collagen and imidazole derivatives
WO2019079089A2 (en) Method to treat antimicrobial resistant candida

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU BB BG BR DK FI JP KP KR LK MC MG MW NO RO SD SU US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE BJ CF CG CH CM DE FR GA GB IT LU ML MR NL SE SN TD TG