AU2002361825A1 - Plaster for the treatment of dysfunctions and disorders of nail growth - Google Patents
Plaster for the treatment of dysfunctions and disorders of nail growthInfo
- Publication number
- AU2002361825A1 AU2002361825A1 AU2002361825A AU2002361825A AU2002361825A1 AU 2002361825 A1 AU2002361825 A1 AU 2002361825A1 AU 2002361825 A AU2002361825 A AU 2002361825A AU 2002361825 A AU2002361825 A AU 2002361825A AU 2002361825 A1 AU2002361825 A1 AU 2002361825A1
- Authority
- AU
- Australia
- Prior art keywords
- nail
- plaster
- contact layer
- adhesive
- skin
- 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
Links
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- 238000011282 treatment Methods 0.000 title claims description 37
- 230000004064 dysfunction Effects 0.000 title claims description 27
- 230000036562 nail growth Effects 0.000 title claims description 22
- 239000000853 adhesive Substances 0.000 claims description 63
- 230000001070 adhesive effect Effects 0.000 claims description 59
- 239000013543 active substance Substances 0.000 claims description 31
- -1 softeners Substances 0.000 claims description 29
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 24
- 239000003961 penetration enhancing agent Substances 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 21
- 239000002904 solvent Substances 0.000 claims description 20
- 239000000654 additive Substances 0.000 claims description 18
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- 201000005882 tinea unguium Diseases 0.000 claims description 17
- 206010028698 Nail dystrophy Diseases 0.000 claims description 15
- 239000003963 antioxidant agent Substances 0.000 claims description 15
- 239000011230 binding agent Substances 0.000 claims description 15
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 15
- 239000000194 fatty acid Substances 0.000 claims description 15
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- 238000011321 prophylaxis Methods 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 14
- 239000004971 Cross linker Substances 0.000 claims description 13
- 239000000945 filler Substances 0.000 claims description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- 208000026721 nail disease Diseases 0.000 claims description 12
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 12
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- DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 claims description 10
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- 125000005456 glyceride group Chemical group 0.000 claims description 8
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- QXHHHPZILQDDPS-UHFFFAOYSA-N 1-{2-[(2-chloro-3-thienyl)methoxy]-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound S1C=CC(COC(CN2C=NC=C2)C=2C(=CC(Cl)=CC=2)Cl)=C1Cl QXHHHPZILQDDPS-UHFFFAOYSA-N 0.000 claims description 5
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- ARIWANIATODDMH-UHFFFAOYSA-N Lauric acid monoglyceride Natural products CCCCCCCCCCCC(=O)OCC(O)CO ARIWANIATODDMH-UHFFFAOYSA-N 0.000 claims description 5
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Description
Plaster for the treatment of dysfunctions and disorders of nail growth
Specification
The present invention relates to plasters for prophylaxis and/or treatment of a dysfunctions or disorders of nail growth, the use of said plasters and methods for prophylaxis and/or treatment of a dysfunction or disorder of nails and/or nail growth using said plasters.
Background of the invention
Plasters for prophylaxis and/or treatment of a dysfunction or disorder of nail growth are not described in the literature while plasters for the treatment of, for example, onychomycosis are known. For instance, WO-A-99/40955 discloses a pressure sensitive adhesive matrix patch for the treatment of onychomycosis. This device for treating fungal infections of toenails and fingernails is made up of an occlusive backing layer and a pressure-sensitive adhesive matrix layer wherein an effective amount of an antifungal agent is uniformly dispersed, optionally with a chemical enhancer. The matrix layer has a first surface adhering to the backing layer and a second surface adapted to be in diffusional contact with the infected nail and surrounding skin area.
A method for treating onychomycosis is described in US-A-5 464 610. Within said method a plaster preparation is used comprising salicylic acid or a salt, ester or mixture thereof. Said plaster preparation is attached to a carrier and the salicylic acid is present in the plaster preparation in an amount ranging from 10 to 80% by weight of the preparation.
Nail evulsion compositions and methods for evulsing nails and treating nail and nail bed infections are disclosed in US-A-5 993 790. Claimed is a topical nail enamel composition comprising water-based nail lacquer, a preservative, urea, and a natural additive. Said nail enamel composition is suitable for the treatment of fungal, yeast, and bacterial infections of the nails and the nail beds.
US-A-5 753 256 discloses a plaster for the treatment of nail mycoses which consists of a flexible covering film, a layer of an acrylate polymer matrix, inseparably linked to said covering film, and comprises an active compound
selected form miconazole, econazole, isoconazole, tioconazole, terconazole, oxiconazole, ketoconazole, itraconazole, tolciclate, sulbentine, haloprogin, griseofulvin, cyclopirox, terbinafin, and salts of these compounds.
It is object of the present invention to provide a plaster for prophylaxis and/or treatment of dysfunctions or disorders of nails, nail structure and/or nail growth which is not due to onychomycosis.
This object is solved by the plaster of the independent claims and the use of said plaster. Further advantageous features, aspects and details of the invention are evident from the dependent claims, the description, and the examples of the present application.
Description of the invention
The present application relates to plasters for prophylaxis and/or treatment of dysfunctions or disorders of nails and/or nail growth. Said plasters comprise a layer being designed to be in close contact with the nail and optionally with the surrounding skin. Said layer comprises: a) an adhesive; b) at least one skin and/or nail permeation enhancer; c) at least one therapeutically effective amount of a pharmaceutically active agent contained in said contact layer; and d) at least one additive selected from the group comprising binders, cross linkers, softeners, solvents, fillers, and/or antioxidants.
Plasters constructed of two or more layers are also useful for the purposes disclosed herein. A preferred embodiment comprises a layer which is separated into a backing layer and a contact layer wherein the contact layer is attached to said backing layer and is designed to be in close contact with the nail and optionally with the surrounding skin. Said contact layer comprises: a) an adhesive; b) at least one skin and/or nail permeation enhancer; c) at least one therapeutically effective amount of a pharmaceutically active agent contained in said contact layer; and d) at least one additive selected from the group comprising binders, cross linkers, softeners, solvents, fillers, and/or antioxidants.
The flexible backing layer holds and presses the plaster against the nail and skin in order to increase migration from the contact layer into the nail, nail beds, and surrounding skin. Furthermore, the backing layer protects the contact layer form being contaminated. A preferred embodiment of said plaster comprises a colorless backing layer or a backing layer having an amber-like color. Another preferred embodiment comprises a flexible and/or occlusive backing layer. The plaster has sufficient flexibility in order to seal the affected nail exactly even if the nail has an uneven surface.
Another preferred embodiment of the present invention comprises a contact layer which is further divided into a central layer and a drug containing layer. The central layer is designed to be in close contact with the backing layer and the drug containing layer and contains no pharmaceutically active agent while the drug containing layer comprises a therapeutically effective amount of a pharmaceutically active agent as summarized below.
The backing layer is preferably made of polyethylene (such as LDPE, Plastotrans®), polypropylene, polyurethane, polyester (such as Revatrans®, TRICON GmbH, Freiburg), Guttagena® PVC NBR foil (such as Guttagena® WK 68, Kalle Pentaplast, Germany), cotton, cotton/viscose, silk, polyethylenterephthalate (such as Hostaphan® RN 36 sil; Hostaphan® RN 100 sil, Loparex, Apeldoorn, The Netherlands), ethylene-methacrylic acid coplymers and/or mixtures of these materials. More preferably are siliconized polymers and/or copolymers.
As used herein, the term "contact layer" refers to a biocompatible adhesive containing said pharmaceutically active agent and optionally further ingredients and/or additives with special biological functions suitable to allow and support migration and penetration of the pharmaceutically active agent into the nails, nail beds, and the associated skin. The contact layer is inseparably linked with the backing layer, preferably with a flexible occlusive backing layer.
A sufficiently large amount of said pharmaceutically active agent can be embedded into said adhesive which is preferably a gel-like or rubber-like adhesive in order to admit and maintain a continuing flow of the pharmaceutically active agent through the skin and nail for a longer time, preferably for one week.
The inventive plaster can be manufactured in any suitable shape, such as round, oval, rectangular or quadratic shape. Preferred plaster sizes are 0.5 cm2, 0.85 cm2, .5 cm2, 2.3 cm2, 2.5 cm2, and 4.0 cm2.
Suitable therapeutically effective amounts of said pharmaceutically active agents are 0.005 - 10 mg per cm2 plaster, preferably 0.01 - 5 mg per cm2 plaster, more preferably 1 - 4 mg, and most preferably 1 - 2 mg per cm2 plaster.
These antifungal agents can roughly by divided into five groups comprising polyenes such as amphotericin B and nystatin; azoles especially imidazoles such as miconazole and sertaconazole; triazoles such as itraconazole, fluconazole, and voriconazole; allylamines such as naftifidine and terbinafine; morpholines such as amorolfine; and benzofuranes such as griseofulvin.
The inventive plaster contains a pharmaceutically active amount of at least one pharmaceutically active agent, such as fluconazole (Diflucan®), butoconazole, enilconazole, fenticonazole, suiconazole, naftifidine, clioquinol, iodoquinol, rimoprogin, griseofulvin, terbinafine (Lamisil®, Novartis Pharma), clotrimazole, itraconazole (Sempera®, Janssen Pharmaceutical ), tioconazole, miconazole, tolnaftate, pyrogallol, econazole, isoconazole, terconazole, oxiconazole, voriconazole, amphotericin B, nystatin, tolciclate, sulbentine, ketoconazole, ciclopirox (Batrafen®, Aventis Pharma), amorolfine, bifonazole, sodium pyrithione, salicylic acid and/or salts of these agents.
The plasters and plaster preparations of the state of the art use these pharmaceutically active agents for the treatment of fungal infections of the nails, i.e. onychomycosis. The present invention reveals now for the first time the use of said pharmaceutically active agents for prophylaxis and/or treatment of dysfunctions or disorders of nails and/or nail growth and destruction of nail structure which are not onychomycosis. Especially, the prophylaxis and/or treatment of onychodystrophy which is not caused by onychomycosis is disclosed.
Onychomycosis, as a fungal infection, is regarded as a subgroup of onychodystrophy. Thus, infections caused by fungi are excluded from the scope of this invention.
Onychodystrophy comprises a number of nail dysfunctions and disorders such as Onychodystrophy comprises a number of nail dysfunctions and disorders such as
onychocryptosis, melanonychia striata, white line disease, chronic paronychia, discolored nails, thickened nails, Unguis inflexus, coilonychia, scleronychia, onychogryphosis, onychauxis, onychoschisis, onychorrhexis, trachyonychia, cleaved and split nails.
Onychodystrophy can be caused or induced by fungal infections (onychomycosis) which is excluded from the scope of this invention.
The most prominent group of onychodystrophy apart from onychomycosis are induced by diseases of the skin such as neurodermitis (atopic eczema), and psoriasis. Furthermore, bacterial or viral infections are capable of causing or inducing onychodystrophy.
Also drugs such as antibiotics, anticoagulative agents, ACE inhibitors, betablockers, thiazides, cytostatic agents and the like are known to cause onychodystrophy. Another reason for onychodystrophy are systemic diseases such as avitaminoses, kidney failure, and heart failure. Another reason for onychodystrophy is the contact with chemical compounds such as acids, bases, oxidants and the like which cause burns, cauterizations, and also physical influences resulting in mechanical destruction of the nail plate. Finally, idiopathic causes exist for dysfunctions and/or disorders of the nail.
As used herein, the term "nail" refers to fingernails and toenails of mammals, especially humans.
A preferred embodiment of said plaster comprises a contact layer designed in such a way that said contact layer seals the affected nail almost perfectly which results in an almost quantitative exclusion of air. Furthermore, the inventive plaster may optionally contain an additional oxygen scavenger. Suitable oxygen scavenger comprise transition metal chelates or complexes with, for instance salicylic acid and/or salicylate and/or polycarboxylic acids, or oxidizable organic acids or alcohols in combination with a catalyzing agent.
Suitable skin and/or nail permeation enhancer are well known to a person skilled in the art and may be selected from the group comprising of fatty acids, fatty acid esters, fatty acid amides, fatty alcohols, 2-(2-ethoxyethoxy)-ethanol, esters of glycerol, glycerol monolaurate, propylene glycol, polyethylene glycols, unsaturated polyglycolized glycerides (Labrafil M1944CS®, Gattefosse), saturated
polyglycerides (Labrasol®, Gattefosse), a partial glyceride of ricinoleic acid (Softigen®, Hϋls), Labrafac Hydro WL1219® (Gattefosse), Estasan® (Gattefosse), α-hydroxy acids, dimethylsulfoxide, decylmethylsulfoxide, pyrrolidones, salicylic acid, lactic acid, myristol, isopropyl myhstate, dimethylformamide, dimethylacetamide, sodium dodecylsulfate, phospholipides, Transcutol® (Gattefosse), Eutanol® (Henkel), as well as mixtures comprising oleic acid / 2-(2- ethoxyethoxy)-ethanol, oleic acid / Labrafil®, and oleic acid / Labrafac® (Gattefosse), preferably in a ratio of approximately 1 :1 , and the like. Also enzyme components, such as proteolytic enzymes which facilitate permeation of chemical substances through the hardened nail or keratin tissue, can be used as permeation enhancer.
Examples for most common fatty acids are capric-, lauric-, myristic-, palmitic-, margaric-, stearic-, arachidic-, behenic-, lignoceric-, myristoleic-, palmitoleic-, petroselinic-, oleic-, vaccenic-, gadoleic-, gondoic-, urucic-, nervonic-, linoleic-, γ- linolenic-, dihomo-γ-linolenic-, arachidonic-, 7,10,13,16-docosatetraenoic-, 4,7,10,13,16-docosapentaenoic-, α-linolenic-, stea donic-, 8,11 ,14,17- eicosatetraenoic-, 5,8,11 ,14,17-eicosapentaenoic-, 7,10,13,16,19- docosapentaenoic-, 4,7,10,13,16,19-docosahexaenoic-, 5,8,11 -eicosatrienoic-, tariric-, santalbic-, stearolic-, 6,9-octadecenynoic-, pyrulic-, crepenynic-, heisteric-, t8,t10-octadecadiene-12-ynoic-, 5,8,11 ,14-eicosatetraynoic-, cerebronic-, hydroxynervonic-, brassylic-, and thapsic acid. Also useful are the lower alkyl ester and amides of said fatty acids or the corresponding alcohols thereof. The glycerol esters may also contain one or more of said fatty acids.
The skin and/or nail permeation enhancer supports and increases the penetration and permeation of said pharmaceutically active agent through the skin and into the nails and nail beds. The term "penetration enhancement" or "permeation enhancement" relates to an increase in the permeability, of a biological membrane or skin and nails. Skin and/or nail permeation enhancer are mostly used for increasing the rate at which a pharmaceutically active ingredient permeates through said membrane. The effect of permeation enhancement can be determined by the use of a diffusion cell apparatus as described by Merrit et al. (Diffusion Apparatus for Skin Penetration, J. Controlled Release, 1984, 1 , 161- 162) measuring the rate of diffusion of a pharmaceutically active agent through animal or human skin.
An effective amount of a skin and/or nail permeation enhancer means an amount sufficient to provide the desired increase in membrane permeability and, accordingly, to obtain the desired depth of penetration and penetration of a sufficient amount of said pharmaceutically active agent.
The inventive plaster preferably contains said skin and/or nail permeation enhancer in the contact layer in an amount of between 0.1% to 30% by weight of the adhesive, preferably 0.1% to 15% by weight of the adhesive, more preferably 0.5% to 10%, and most preferably 0.7% to 6% by weight of the contact layer.
The inventive plaster comprises optionally further additives selected from the group comprising binders, cross linkers, softeners, solvents, fillers, and/or antioxidants.
Said additive or said additives, if present, are contained in the layer in an amount of between 2% to 80% by weight of the contact layer, preferably 5% to 40% by weight of the contact layer, more preferably between 8% to 30%, even more preferably between 12% to 25%, and most preferably in an amount between 15% to 20% by weight of the contact layer.
Binders characterize substances that bind or "glue" powders together and make them cohesive by forming the adhesive layer, thus serving as a further "adhesive" in the formulation. Suitable binders include non-natural sugars, natural sugars such as sucrose, starches derived from wheat, com rice and potato; synthetic and , natural gums such as acacia, gelatin and tragacanth; derivatives of seaweed such as alginic acid, sodium alginate and ammonium calcium alginate; cellulosic materials such as methylcellulose and sodium carboxymethylcellulose and hydroxypropyl-methylcellulose; polyvinylpyrrolidone; and inorganics such as magnesium aluminum silicate, polyethylene glycol and waxes.
If present, the amount of binder in the adhesive can range from about 1 to 50% by weight of the adhesive, preferably from about 10 to about 50% by weight of the adhesive, more preferably from about 20 to about 50% by weight, even more preferably from about 30 to about 40% by weight.
Cross linkers may be selected from the group comprising cross linking agents such as aluminum acetylacetonate, acrylate-vinylacetate copolymer, aluminum acetonate, titanium acetylacetonate, titanium acetonate, and succinic acid.
If present, the amount of cross linkers in the adhesive can range from about 0.01 to 30% by weight of the adhesive, preferably from about 0.1 to about 50% by weight of the adhesive, more preferably from about 10 to about 50% by weight, even more preferably from about 30 to about 40% by weight.
Softener may be chosen from the group comprising dibutylsebacate (DBS), Macrogol® (Clariant, Frankfurt, Germany) and the like.
If present, the amount of softener in the adhesive can range from about 0.001 to 25% by weight of the adhesive, preferably from about 0.01 to about 10% by weight of the adhesive, more preferably from about 0.1 to about 6% by weight, even more preferably from about 0.5 to about 3% by weight.
Suitable solvents for the inventive plaster may be selected form purified water; ketones such as acetone, butanone, 2-pentanone, 3-pentanone; alcohols such as ethanol, propanol, isopropanol, butanol, isobutanol, sec.-butanol, tert.-butanol; esters such as acetic acid ethyl ester, acetic acid propyl ester and the like. Furthermore, mixtures of said solvents can also be used. Suitable co-solvents may be used together with the above-mentioned solvents or mixtures of solvents, said co-solvents may be selected from the group comprising lactic acid, salicylic acid, succinic acid, urea, Miglyol® 812 (Chemische Werke Hϋls, Marl, Germany), triglycerides, ethyloleate, glycerylmonododecanoate, olein, oleate, Macrogol® 6000, and lecithin.
If present, the amount of solvents or the total amount of solvents and co-solvents in the adhesive can range from about 0.5 to 70% by weight of the adhesive, preferably from about 3 to about 60% by weight of the adhesive, more preferably from about 10 to about 50% by weight, even more preferably from about 20 to about 40% by weight, and most preferably from about 10 to about 30% by weight of the adhesive.
Fillers may be chosen from the group comprising silica, silicic acid, preferably colloidal silica and colloidal silicic acid, lactose, Aerosil® such as Aerosil® 200 (Degussa-Hϋls, Frankfurt, Germany), starch, Bentonit® (Sϋdchemie, Mannheim, Germany) and the like.
If present, the amount of fillers in the adhesive can range from about 0.01 to 15% by weight of the adhesive, preferably from about 0.1 to about 10% by weight of the adhesive, more preferably from about 0.3 to about 6% by weight, even more preferably from about 0.5 to about 3% by weight.
Butylhydroxytoluene (BHT) may be mentioned as an example for a suitable antioxidant. Antioxidants are well known to a person skilled in the art and may be selected form the antioxidants of the state of the art.
If present, the amount of antioxidants in the adhesive can range from about 0.001 to 10% by weight of the adhesive, preferably from about 0.005 to about 6% by weight of the adhesive, more preferably from about 0.01 to about 3% by weight, even more preferably from about 0.05 to about 1 % by weight.
Suitable adhesives for the inventive plaster may comprise acrylic copolymers, also known as "acrylic adhesives", like National Starch Durotak® 80-1196, National Starch Durotak® 387-2825, or Monsanto Gelya 737; polyacrylamide; rubber- based adhesives, also called "rubber adhesives", such as polyisobutylene (PIB) (e.g. Adhesive Research MA-24), polyisoprene, styrene-isoprene copolymers, or urethane rubbers; and silicone based adhesives, so called "silicone adhesives", such as Dow Bio-PSA.
The adhesives that may be used according to the invention represent a polymer, preferably an acrylate copolymer. Suitable monomers or mixtures of monomers for the manufacture of said acrylate polymer comprise methyl acrylate, methyl methacrylate, butyl acrylate, butyl methacrylate, isooctyl acrylate, isooctyl methacrylate, aminoalkyl acrylate, aminoalkyl methacrylate, aminoalkyl methacrylate copolymers (such as EUDRAGIT® E 100, EUDRAGIT® RL, EUDRAGIT® RS, EUDRAGIT® NE 30 D. commercially available from Rohm, Degussa-Hϋls Group), hydroxyethyl acrylate, hydroxyethyl methacrylate, 2- ethylhexyl acrylate, 2-ethylhexyl methacrylate, acrylic acid, methacrylic acid, vinyl acetale, and glycidyl methacrylate. Acrylate-based adhesives are commercially available from National Starch Chemical B. V., Zutphen, NL, under the name Durotak®. Examples of said product class are Durotak® 280-2287 (51% solution or solid matter), Durotak® 326-1753 (37% solution or solid matter), Durotak® 280- 1753 (33% solution or solid matter), Durotak® 901-1052 (48% solution or solid matter), Durotak® 80-1196 (solid matter), and Durotak® 387-2825 (50% solution).
The adhesive is contained in the plaster of the present invention in an amount of between 40% to 95% by weight of the plaster, preferably between 60 to 90%, more preferably between 70% to 90%, and most preferably between 80% to 90% by weight of the plaster.
The present invention discloses a combination therapy wherein the plaster is used in combination with a systemic treatment of onychomycosis or other systemic treatments for dysfunctions or disorders of nails and/or nail growth.
Said combination therapy is especially useful for prophylaxis and/or treatment of onychomycosis, onychocryptosis, nail psoriasis, melanonychia striata, white line disease, eczema, chronic onychia, discolored nails, thickened nails, and onychodystrophy.
As used herein, the term "plaster" refers to any device which can be applied to the nail and which comprises a contact layer which is pressed against the nail surface. Suitable plaster devices include plasters or preformed films based upon rubbers, acrylics, urethanes, silicone materials, polyvinylalkylethers, gels, and impregnated microporous membranes. Said plaster device could also be combined with or incorporated or formed into shape of an artificial or fake nail in order to improve cosmetic appearance.
As used herein, the term "plaster" refers to a preparation of at least one pharmaceutically active agent, optionally together with suitable additives and/or binders, in a plaster device.
Furthermore, the present invention describes the use of the plaster for the transdermal and/or transnail prophylaxis and/or treatment of a dysfunction or disorder of nails and/or nail growth by adhesively securing to the nail and optionally the surrounding skin of said nail the plaster comprising a layer being designed to be in close contact with the nail and optionally with the surrounding skin. Said layer comprises: a) an adhesive; b) at least one skin and/or nail permeation enhancer; c) at least one therapeutically effective amount of a pharmaceutically active agent contained in said contact layer; and d) at least one additive selected from the group comprising binders, cross linkers, softeners, solvents, fillers, and/or antioxidants.
Instead of the above-mentioned plaster the embodiment comprising two or more layer can also be used in order prevent and/or a dysfunction or disorder of nails and/or nail growth by adhesively securing to the nail and optionally the surrounding skin of said nail the plaster comprising: a) a backing layer; and b) a contact layer attached to said backing layer and being designed to be in close contact with the nail and optionally with the surrounding skin; said contact layer comprising: aa) an adhesive; bb) at least one skin and/or nail permeation enhancer; cc) at least one therapeutically effective amount of a pharmaceutically active agent contained in said contact layer; and dd) at least one additive selected from the group comprising binders, cross linkers, softeners, solvents, fillers, and/or antioxidants.
One important aspect of the present invention is that the use of the plasters does not require the procedure of drilling at least one hole into the nail and/or daily scraping of the nail. Another advantage of the present invention is that the plasters are easy to use, convenient and user-friendly.
Furthermore, the inventive plaster can be used in combination with a systemic treatment of a dysfunction or disorder of nails and/or nail growth, such as onychomycosis, onychocryptosis, nail psoriasis, melanonychia striata, white line disease, eczema, chronic onychia, discolored nails, thickened nails, and onychodystrophy.
The present invention discloses a method for the transdermal and/or transnail delivery of a sufficient amount of at least one pharmaceutically active agent to an affected nail, nail bed and surrounding tissue by adhesively securing to the nail and optionally the surrounding skin the plaster, in order to treat a dysfunction or disorder of growth of said nail.
One advantage of said inventive method is exhibited by the fact that this method does not require drilling holes into the nails and/or daily scraping of the nails.
The inventive method can also be applied in combination with a systemic treatment of onychomycosis or other systemic treatments for dysfunctions or
disorders of nails and/or nail growth. Especially, a combination of the inventive method with a systemic treatment of onychomycosis or other systemic treatments for dysfunctions or disorders has been proven effective.
Examples
The following examples shall exemplify the present invention and shall not limit the scope of the present invention to these specific embodiments.
The plasters or nail patches may preferably comprise a backing layer and/or a release liner. The backing layer, if present, is preferably made from PVC such as Guttagena PVC NBR foil and the release liner is preferably made of PET such as PET foil with both sides siliconized (100 μm).
Example 1
Plaster 1 : Compounds of the contacting layer for 1.0 cm2 plaster
The efficacy of the plaster was investigated in patients suffering from onychodystrophy of the fingernails.
One patient had a 40% dystrophic nail involvement at the start of treatment, which could be decreased to 15% after 24 weeks of treatment with the plaster. Another patient was treated for 24 weeks and the dystrophic nail area could be decreased from 20% to 5%. Another patient was also treated for 24 weeks with the plaster and the affected nail area was decreased from 30% to 10%.
Few treated patients showed only minor side effects during the treatment period. Said side effects were characterized as skin scaling of the tissue surrounding the nails.
One advantageous effect of the plasters disclosed herein is that the plaster has only to be replaced every week and not, for instance, daily. Therefore, an excess of the antimycotic agent is used in order to ensure that a sufficient amount of the
antimycotic agent will after one week still be present in the adhesive layer of the plaster. The remaining amount of the antimycotic agent in the plaster has a prophylactic effect and prevents the development of infections and diminishes the risk of third persons to be infected by the patient.
The plasters 2 - 6 according to examples 2 - 6 give similar results.
The treatment period can last in isolated cases one year or longer. Normally, the treatment period will be one to several months under the condition that the plaster is replaced weekly.
Example 2:
Plaster 2: Composition for the manufacture of 1 cm2 plaster
The compound will be weighed and stirred until homogeneity. The mixture will be applied to a siliconized polyester sheet (thickness 75 μm, from Loparex, Apeldorn, NL). The wet thickness of the glue film amounts 400 μm. Following 15 minutes drying at 60°C in drying cabinet and storage at 25°C for 12 hours the glue layer will be covered with polyolefine film of 50 μm thickness (Cotran No. 9722, from 3M-Medica, Borken, Germany).
Finally the self-adhesive plaster in the size of finger or toe nails will be punched from the sheet.
Example 3:
Plaster 3: Composition for the manufacture of 1 cm2 plaster
No. Compound Amount
Ciclopirox 1.8 mg
Durotak 36-6172 solution (57.1 %) 14 mg n-Heptan 2 mg
The compound will be weighed and stirred until homogeneity. The mixture will be applied to a siliconized polyester sheet (thickness 75 μm, from Loparex, Apeldorn, NL). The wet thickness of the glue film amounts 400 μm. Following 15 minutes drying at 60°C in drying cabinet and storage at 25°C for 12 hours the glue layer will be covered with polyolefine film of 50 μm thickness (Cotran No. 9722, from 3M-Medica, Borken, Germany).
Finally the self-adhesive plaster in the size of finger or toe nails will be punched from the sheet.
Example 4:
Plaster 4: Composition for the manufacture of 1 cm2 plaster
The compound will be weighed and stirred until homogeneity. The mixture will be applied to a siliconized polyester sheet (thickness 75 μm, from Loparex, Apeldorn, NL). The wet thickness of the glue film amounts 400 μm. Following 15 minutes drying at 70°C in drying cabinet and storage at 25°C for 12 hours the glue layer will be covered with polyolefine film of 50 μm thickness (Cotran No. 9722, from 3M-Medica, Borken, Germany).
Finally the self-adhesive plaster in the size of finger or toe nails will be punched from the sheet.
Example 5:
Plaster 5: Composition for the manufacture of 1 cm2 plaster
The compound will be weighed and stirred until homogeneity. The mixture will be applied to a siliconized polyester sheet (thickness 75 μm, from Loparex, Apeldorn, NL). The wet thickness of the glue film amounts 400 μm. Following 15 minutes drying at 60°C and 10 minutes at 80°C in drying cabinet and storage after cooling the glue layer will be covered with polyolefine film of 50 μm thickness (Cotran No. 9722, from 3M-Medica, Borken, Germany).
Finally the self-adhesive plaster in the size of finger or toe nails will be punched from the sheet.
Example 6:
Plaster 6: Compounds of the contacting layer for 1.0 cm2 plaster
Equipment:
The solution is prepared in a high-speed stirred tank. The stirrer may be a dissolver disc, for example, which guarantees thorough mixing also at rising viscosity. On a laboratory scale, coating and drying are performed in a laboratory coating unit with integrated dryer (LTSV/LTF by W. Mathis AG, Switzerland).
Instructions for processing:
Acetone, isopropanol, and ethanol is placed in a stirred tank and EUDRAGIT® E 100 is added in portions over a period of 90 minutes. The stirrer is set to a speed which excludes sediment formation while dissolving EUDRAGIT® E 100. Dibutylsebacate is added swiftly and stirring is continued for another 20 minutes. Thereafter fluconazole is added and succinic acid is given to the polymer solution
in portions with intensive stirring. After complete addition of succinic acid the polymer solution is stirred for additional 20 minutes.
Coating is performed with the final polymer solution at the following parameters: Coating: approximately 100 g of said polymer solution is applied to the backing layer foil (15 μm thickness, Revatrans ® MN, Tricon GmbH Freiburg) by means of a rotary doctor blade at a nip of 200 μm. Drying: Drying is performed at 60°C for 10 minutes, circulating air: 1500 m3/h, exhaust air: 80 m /h.
Claims (3)
1. Plaster for prophylaxis and/or treatment of dysfunctions or disorders of nails and/or nail growth comprising: a layer being designed to be in close contact with the nail and optionally with the surrounding skin; said layer comprising: a) an adhesive; b) at least one skin and/or nail permeation enhancer; c) at least one therapeutically effective amount of a pharmaceutically active agent contained in said contact layer; and d) at least one additive selected from the group comprising binders, cross linkers, softeners, solvents, fillers, and/or antioxidants.
2. Plaster for prophylaxis and/or treatment of dysfunctions or disorders of nails and/or nail growth comprising: a) a backing layer; and b) a contact layer attached to said backing layer and being designed to be in close contact with the nail and optionally with the surrounding skin; said contact layer comprising: aa) an adhesive; bb) at least one skin and/or nail permeation enhancer; cc) at least one therapeutically effective amount of a pharmaceutically active agent contained in said contact layer; and dd) at least one additive selected from the group comprising binders, cross linkers, softeners, solvents, fillers, and/or antioxidants.
3. Plaster according to claim 2 wherein said backing layer is an occlusive backing layer.
4. Plaster according to any one of claims 1 - 3 wherein the skin and/or nail permeation enhancer is selected from the group comprising fatty acids, fatty acid esters, fatty acid amides, fatty alcohols, 2-(2-ethoxyethoxy)-ethanol, esters of glycerol, glycerol monolaurate, propylene glycol, polyethylene glycols, unsaturated polyglycolized glycerides, saturated polyglycerides, a partial glyceride of ricinoleic acid, α-hydroxy acids, dimethylsulfoxide, decylmethylsulfoxide, pyrrolidones, salicylic acid, lactic acid, myristol, isopropyl myristate, dimethylformamide, dimethylaceta ide, sodium dodecylsulfate, phospholipides, and proteolytic enzymes.
5. Plaster according to any one of claims 1 - 4 wherein the skin and/or nail permeation enhancer is contained in the contact layer in an amount of between 0.7% to 6% by weight of the contact layer.
6. Plaster according to any one of claims 1 - 5 wherein the additives are contained in the contact layer in an amount of between 15% to 20% by weight of the contact layer.
7. Plaster according to any one of claims 1 - 6 wherein said pharmaceutically active agent is selected from the group comprising fluconazole (Diflucan®), butoconazole, enilconazole, fenticonazole, sulconazole, naftifidine, clioquinol, iodoquinol, rimoprogin, griseofulvin, terbinafine (Lamisil®, Novartis
Pharma), clotrimazole, itraconazole (Sempera®, Janssen Pharmaceutical ), tioconazole, miconazole, tolnaftate, pyrogallol, econazole, isoconazole, terconazole, oxiconazole, voriconazole, amphotericin B, nystatin, tolciclate, sulbentine, ketoconazole, ciclopirox (Batrafen®, Aventis Pharma), amorolfine, bifonazole, sodium pyrithione, salicylic acid and/or salts of these agents.
8. Plaster according to any one of claims 1 - 7 wherein said pharmaceutically active agent is contained in the adhesive in an amount of between 0.01 - 5 mg per cm2 plaster.
9. Plaster according to any one of claims 1 - 8 wherein the adhesive is selected from the group comprising acrylic adhesives, rubber adhesives, and silicone adhesives.
10. Plaster according to any one of claims 1 - 9 wherein the adhesive is contained in the plaster in an amount of between 80% to 90% by weight of the contact layer.
11. Combination therapy wherein the plaster is used in combination with a systemic treatment of a dysfunction or disorder of nails and/or nail growth.
12. Use of the plaster for the transdermal and/or transnail prophylaxis and/or treatment of a dysfunction or disorder of nails and/or nail growth by adhesively securing to the nail and optionally the surrounding skin of said nail the plaster comprising: a layer being designed to be in close contact with the nail and optionally with the surrounding skin; said layer comprising: a) an adhesive; b) at least one skin and/or nail permeation enhancer; c) at least one therapeutically effective amount of a pharmaceutically active agent contained in said contact layer; and d) at least one additive selected from the group comprising binders, cross linkers, softeners, solvents, fillers, and/or antioxidants.
13. Use of the plaster for the transdermal and/or transnail prophylaxis and/or treatment of a dysfunction or disorder of nails and/or nail growth by adhesively securing to the nail and optionally the surrounding skin of said nail the plaster comprising: a) a backing layer; and b) a contact layer attached to said backing layer and being designed to be in close contact with the nail and optionally with the surrounding skin; said contact layer comprising: aa) an adhesive; bb) at least one skin and/or nail permeation enhancer; cc) at least one therapeutically effective amount of a pharmaceutically active agent contained in said contact layer; and dd) at least one additive selected from the group comprising binders, cross linkers, softeners, solvents, fillers, and/or antioxidants.
14. Use according to claim 13 wherein said backing layer is an occlusive backing layer.
15. Use of the plaster according to any one of claims 12 - 14 wherein the skin and/or nail permeation enhancer is selected from the group comprising fatty acids, fatty acid esters, fatty acid amides, fatty alcohols, 2-(2-ethoxyethoxy)- ethanol, esters of glycerol, glycerol monolaurate, propylene glycol, polyethylene glycols, unsaturated polyglycolized glycerides, saturated polyglycerides, a partial glyceride of ricinoleic acid, α-hydroxy acids, dimethylsulfoxide, decylmethylsulfoxide, pyrrolidones, salicylic acid, lactic acid, myristol, isopropyl myristate, dimethylformamide, dimethylacetamide, sodium dodecylsulfate, phospholipides, and proteolytic enzymes.
16. Use of the plaster according to any one of claims 12 - 15 wherein the skin and/or nail permeation enhancer is contained in the contact layer in an amount of between 0.7% to 6% by weight of the contact layer.
17. Use of the plaster according to any one of claims 12 - 16 wherein the additives are contained in the contact layer in an amount of between 15% to 20% by weight of the contact layer.
18. Use of the plaster according to any one of claims 12 - 17 wherein said pharmaceutically active agent is selected from the group comprising fluconazole (Diflucan®), butoconazole, enilconazole, fenticonazole, sulconazole, naftifidine, clioquinol, iodoquinol, rimoprogin, griseofulvin, terbinafine (Lamisil®, Novartis Pharma), clotrimazole, itraconazole (Sempera®, Janssen Pharmaceutical ), tioconazole, miconazole, tolnaftate, pyrogallol, econazole, isoconazole, terconazole, oxiconazole, voriconazole, amphotericin B, nystatin, tolciclate, sulbentine, ketoconazole, ciclopirox (Batrafen®, Aventis Pharma), amorolfine, bifonazole, sodium pyrithione, salicylic acid and/or salts of these agents.
19. Use of the plaster according to any one of claims 12 - 18 wherein said pharmaceutically active agent is contained in the adhesive in an amount of between 0.01 - 5 mg per cm2 plaster.
20. Use of the plaster according to any one of claims 12 - 19 wherein the adhesive is selected from the group comprising acrylic adhesives, rubber adhesives, and silicone adhesives.
21. Use of the plaster according to any one of claims 12 - 20 wherein the adhesive is contained in the plaster in an amount of between 80% to 90% by weight of the contact layer.
22. Use of the plaster according to any one of claims 12 - 21 in combination with a systemic treatment of a dysfunction or disorder of nails and/or nail growth, especially of onychomycosis, onychocryptosis, nail psoriasis, melanonychia striata, white line disease, eczema, chronic onychia, discolored nails, thickened nails, and other forms of onychodystrophy.
23. Method for the transdermal and/or transnail prophylaxis and/or treatment of a dysfunction or disorder of nails and/or nail growth by adhesively securing to the nail and optionally the surrounding skin of said nail the plaster comprising: a layer being designed to be in close contact with the nail and optionally with the surrounding skin; said layer comprising: a) an adhesive; b) at least one skin and/or nail permeation enhancer; c) at least one therapeutically effective amount of a pharmaceutically active agent contained in said contact layer; and d) at least one additive selected from the group comprising binders, cross linkers, softeners, solvents, fillers, and/or antioxidants.
24. Method for the transdermal and/or transnail prophylaxis and/or treatment of a dysfunction or disorder of nails and/or nail growth by adhesively securing to the nail and optionally the surrounding skin of said nail the plaster comprising: a) a backing layer; and b) a contact layer attached to said backing layer and being designed to be in close contact with the nail and optionally with the surrounding skin; said contact layer comprising: aa) an adhesive; bb) at least one skin and/or nail permeation enhancer; cc) at least one therapeutically effective amount of a pharmaceutically active agent contained in said contact layer; and dd) at least one additive selected from the group comprising binders, cross linkers, softeners, solvents, fillers, and/or antioxidants.
25. Method according to claim 24 wherein said backing layer is an occlusive backing layer.
26. Method according to any one of claims 23 - 25 wherein the skin and/or nail permeation enhancer is selected from the group comprising fatty acids, fatty acid esters, fatty acid amides, fatty alcohols, 2-(2-ethoxyethoxy)-ethanol, esters of glycerol, glycerol monolaurate, propylene glycol, polyethylene glycols, unsaturated polyglycolized glycerides, saturated polyglycerides, a partial glyceride of ricinoleic acid, α-hydroxy acids, dimethylsulfoxide, decylmethylsulfoxide, pyrrolidones, salicylic acid, lactic acid, myristol, isopropyl myristate, dimethylformamide, dimethylacetamide, sodium dodecylsulfate, phospholipides, and proteolytic enzymes.
27. Method according to any one of claims 23 - 26 wherein the skin and/or nail permeation enhancer is contained in the contact layer in an amount of between 0.7% to 6% by weight of the contact layer.
28. Method according to any one of claims 23 - 27 wherein the additives are contained in the contact layer in an amount of between 15% to 20% by weight of the contact layer.
29. Method according to any one of claims 23 - 28 wherein said pharmaceutically active agent is selected from the group comprising fluconazole (Diflucan®), butoconazole, enilconazole, fenticonazole, sulconazole, naftifidine, clioquinol, iodoquinol, rimoprogin, griseofulvin, terbinafine (Lamisil®, Novartis Pharma), clotrimazole, itraconazole
(Sempera®, Janssen Pharmaceutical ), tioconazole, miconazole, tolnaftate, pyrogallol, econazole, isoconazole, terconazole, oxiconazole, voriconazole, amphotericin B, nystatin, tolciclate, sulbentine, ketoconazole, ciclopirox (Batrafen®, Aventis Pharma), amorolfine, bifonazole, sodium pyrithione, salicylic acid and/or salts of these agents.
30. Method according to any one of claims 23 - 29 wherein said pharmaceutically active agent is contained in the adhesive in an amount of between 0.01 - 5 mg per cm2 plaster.
31. Method according to any one of claims 23 - 30 wherein the adhesive is selected from the group comprising acrylic adhesives, rubber adhesives, and silicone adhesives.
32. Method according to any one of claims 23 - 31 wherein the adhesive is contained in the plaster in an amount of between 80% to 90% by weight of the contact layer.
3. Method according to any one of claims 23 - 32 in combination with a systemic treatment of a dysfunction or disorder of nails and/or nail growth, especially of onychomycosis, onychocryptosis, nail psoriasis, melanonychia striata, white line disease, eczema, chronic onychia, discolored nails, thickened nails, and other forms of onychodystrophy.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01121202.4 | 2001-09-04 | ||
| EP01121202 | 2001-09-04 | ||
| PCT/EP2002/009912 WO2003020250A1 (en) | 2001-09-04 | 2002-09-04 | Plaster for the treatment of dysfunctions and disorders of nail growth |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002361825A1 true AU2002361825A1 (en) | 2003-06-05 |
| AU2002361825B2 AU2002361825B2 (en) | 2007-01-25 |
Family
ID=8178546
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002361825A Ceased AU2002361825B2 (en) | 2001-09-04 | 2002-09-04 | Plaster for the treatment of dysfunctions and disorders of nail growth |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US20040265362A1 (en) |
| EP (1) | EP1423102B1 (en) |
| JP (1) | JP4806162B2 (en) |
| KR (1) | KR100757611B1 (en) |
| CN (1) | CN1703206A (en) |
| AU (1) | AU2002361825B2 (en) |
| BR (1) | BR0212304A (en) |
| CA (1) | CA2459483C (en) |
| CY (1) | CY1107284T1 (en) |
| CZ (1) | CZ301310B6 (en) |
| DE (1) | DE60223694T2 (en) |
| DK (1) | DK1423102T3 (en) |
| ES (1) | ES2299630T3 (en) |
| IL (2) | IL160550A0 (en) |
| MX (1) | MXPA04001833A (en) |
| NO (1) | NO20040936L (en) |
| NZ (1) | NZ531406A (en) |
| PL (1) | PL205576B1 (en) |
| PT (1) | PT1423102E (en) |
| RU (1) | RU2302857C2 (en) |
| WO (1) | WO2003020250A1 (en) |
| ZA (1) | ZA200401445B (en) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL160550A0 (en) * | 2001-09-04 | 2004-07-25 | Trommsdorff Arzneimittel | Plaster for the treatment of dysfunctions and disorders of nail growth |
| US7615238B2 (en) * | 2001-09-04 | 2009-11-10 | Trommsdorff GmbH & Co. KG Arzneimitttel | Plaster for the treatment of dysfunctions and disorders of nails, comprising sertaconazole |
| FR2867978B1 (en) * | 2004-03-29 | 2009-02-20 | Galderma Res & Dev | AMOROLFIN PATCH FOR THE TREATMENT OF ONYCHOMICOSIS |
| FR2871692B1 (en) * | 2004-06-22 | 2007-08-03 | Epitact Md Sa | METHOD AND DEVICE FOR ACCELERATING THE GROWTH OF PHANES, IN PARTICULAR NAILS |
| US7740875B2 (en) * | 2004-10-08 | 2010-06-22 | Mediquest Therapeutics, Inc. | Organo-gel formulations for therapeutic applications |
| JP4992181B2 (en) * | 2004-12-28 | 2012-08-08 | 大正製薬株式会社 | External preparation composition |
| EP1893159B1 (en) | 2005-06-17 | 2015-09-30 | Vital Health Sciences Pty Ltd. | A carrier comprising one or more di- and/or monophosphate derivatives of electron transfer agents |
| GT200600411A (en) * | 2005-09-13 | 2007-05-21 | Novartis Ag | COMBINATIONS THAT INCLUDE AN INHIBITOR OF THE RECEIVER OF THE VASCULAR ENDOTELIAL GROWTH FACTOR |
| US8771726B2 (en) * | 2006-08-28 | 2014-07-08 | Hisamitsu Pharmaceutical Co., Inc | Nail patch |
| WO2008105038A1 (en) * | 2007-02-23 | 2008-09-04 | Nichiban Company Limited | Adhesive patch for mycosis |
| PL3441054T3 (en) * | 2007-11-05 | 2021-05-04 | Abigo Medical Ab | Device for the treatment of vaginal fungal infection |
| US8263115B2 (en) * | 2008-09-11 | 2012-09-11 | Abigo Medical Ab | Method and a product to reduce and treat problems associated with tinea pedis |
| US10893983B2 (en) | 2008-12-03 | 2021-01-19 | Abigo Medical Ab | Method for dressing a wound |
| EP2544659A2 (en) | 2009-12-23 | 2013-01-16 | Nuvo Research Inc. | Highly permeating terbinafine formulation for treating onychomycosis |
| EP2531047B1 (en) | 2010-02-05 | 2024-11-13 | Phosphagenics Limited | Carrier comprising non-neutralised tocopheryl phosphate |
| JPWO2011096566A1 (en) | 2010-02-05 | 2013-06-13 | 久光製薬株式会社 | Patch for treatment of onychomycosis |
| MX2012010684A (en) | 2010-03-17 | 2012-11-06 | Novaliq Gmbh | Pharmaceutical composition for treatment of increased intraocular pressure. |
| WO2011120084A1 (en) | 2010-03-30 | 2011-10-06 | Phosphagenics Limited | Transdermal delivery patch |
| EP2462921A1 (en) | 2010-11-11 | 2012-06-13 | Novaliq GmbH | Liquid pharmaceutical compositions for the treatment of a posterior eye disease |
| WO2012122586A1 (en) | 2011-03-15 | 2012-09-20 | Phosphagenics Limited | New composition |
| RU2483749C2 (en) * | 2011-04-15 | 2013-06-10 | Леонид Леонидович Клопотенко | Pharmaceutical composition containing insulin and liposomes for topical application in form of biofilm |
| RU2483748C2 (en) * | 2011-04-15 | 2013-06-10 | Леонид Леонидович Клопотенко | Pharmaceutical composition containing insulin and liposomes for topical application in form of plaster |
| KR101773648B1 (en) * | 2011-05-25 | 2017-08-31 | 노바리크 게엠베하 | Pharmaceutical composition for administration to nails |
| DK2714010T3 (en) | 2011-05-25 | 2017-06-12 | Novaliq Gmbh | TOPICAL PHARMACEUTICAL COMPOSITION BASED ON SEMIFLUORED ALKANES |
| MX361681B (en) | 2012-01-23 | 2018-12-13 | Novaliq Gmbh | Stabilised protein compositions based on semifluorinated alkanes. |
| BR112015004997B1 (en) | 2012-09-12 | 2022-09-13 | Novaliq Gmbh | OPHTHALMIC COMPOSITIONS CONTAINING MIXTURES OF SEMI-FLUORORATED ALKANES |
| PL2895144T3 (en) | 2012-09-12 | 2017-07-31 | Novaliq Gmbh | Semifluorinated alkane compositions |
| JP6503349B2 (en) | 2013-07-23 | 2019-04-17 | ノバリック ゲーエムベーハー | Stabilized antibody composition |
| DK3355990T3 (en) | 2015-09-30 | 2019-09-16 | Novaliq Gmbh | SEMIFLUORINATED COMPOUNDS AND THEIR COMPOSITIONS |
| EP3356313B1 (en) | 2015-09-30 | 2020-05-06 | Novaliq GmbH | 2-perfluorohexyl octane for ophthalmic administration |
| US10973761B2 (en) | 2015-12-09 | 2021-04-13 | Phosphagenics Limited | Pharmaceutical formulation |
| DK3442480T3 (en) | 2016-06-23 | 2020-01-13 | Novaliq Gmbh | PROCEDURE FOR TOPICAL SUBMISSION |
| CN116172987A (en) | 2016-09-22 | 2023-05-30 | 诺瓦利克有限责任公司 | Pharmaceutical composition for treating blepharitis |
| CA3036306C (en) | 2016-09-23 | 2024-05-14 | Novaliq Gmbh | Ophthalmic compositions comprising ciclosporin |
| JP7198754B2 (en) | 2016-12-21 | 2023-01-04 | アベーチョ バイオテクノロジー リミテッド | Method |
| CA3058097C (en) | 2017-04-21 | 2024-01-02 | Novaliq Gmbh | Iodine compositions |
| CN110650734B (en) | 2017-05-12 | 2024-11-15 | 诺瓦利克有限责任公司 | Pharmaceutical compositions comprising semifluorinated alkanes for treating contact lens related conditions |
| WO2019063551A1 (en) | 2017-09-27 | 2019-04-04 | Novaliq Gmbh | Ophthalmic compositions comprising latanoprost for use in the treatment of ocular diseases |
| CN111182893A (en) | 2017-10-04 | 2020-05-19 | 诺瓦利克有限责任公司 | Ophthalmic composition comprising F6H8 |
| WO2019166631A1 (en) | 2018-03-02 | 2019-09-06 | Novaliq Gmbh | Pharmaceutical compositions comprising nebivolol |
| JP2021522219A (en) | 2018-04-27 | 2021-08-30 | ノバリック ゲーエムベーハー | Ophthalmic composition containing tafluprost for the treatment of glaucoma |
| DE102018115270B4 (en) * | 2018-06-26 | 2022-07-14 | Vinederm GmbH | Gel and patch preparation for topical treatment of skin and/or nail disorders |
| US11510855B2 (en) | 2018-09-27 | 2022-11-29 | Dermaliq Therapeutics, Inc. | Topical sunscreen formulation |
| JP7360452B2 (en) | 2018-09-27 | 2023-10-12 | ダーマリック セラピューティクス， インコーポレーテッド | Lipid barrier repair |
| CA3112031A1 (en) | 2018-10-12 | 2020-04-16 | Novaliq Gmbh | Ophthalmic composition for treatment of dry eye disease |
| RU2717086C1 (en) * | 2019-01-31 | 2020-03-18 | Федеральное государственное бюджетное учреждение науки Ордена Трудового Красного Знамени Институт нефтехимического синтеза им. А.В. Топчиева Российской академии наук (ИНХС РАН) | Method of producing base for plasters and gels (embodiments) |
| RU2769437C1 (en) * | 2021-07-08 | 2022-03-31 | Светлана Николаевна Абрамова | Method for restoring nail growth |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5181914A (en) * | 1988-08-22 | 1993-01-26 | Zook Gerald P | Medicating device for nails and adjacent tissue |
| US5464610A (en) * | 1992-10-15 | 1995-11-07 | Schering-Plough Healthcare Products, Inc. | Method for treating onychomycosis |
| RU2076754C1 (en) * | 1992-11-24 | 1997-04-10 | Государственное научно-производственное предприятие "Исток" | Method of treatment of onychodystrophy |
| DE4337945A1 (en) * | 1993-11-06 | 1995-05-11 | Labtec Gmbh | Plasters for the treatment of nail mycoses |
| US5696164A (en) * | 1994-12-22 | 1997-12-09 | Johnson & Johnson Consumer Products, Inc. | Antifungal treatment of nails |
| US5861142A (en) * | 1996-03-25 | 1999-01-19 | Schick; Mary Pichler | Method for promoting hair, nail, and skin keratinization |
| JP2001502317A (en) * | 1996-10-16 | 2001-02-20 | アイ・ピー・アール・インシティチュート・フォー・ファーマシューティカル・リサーチ・エー・ジー | New carrier system |
| US6727401B1 (en) * | 1998-02-12 | 2004-04-27 | Watson Pharmaceuticals, Inc. | Pressure sensitive adhesive matrix patch for the treatment of onychomycosis |
| DE59911740D1 (en) * | 1998-09-10 | 2005-04-14 | Bioequal Ag Muttenz | TOPIC APPLICABLE AGENTS AGAINST NAIL MUSHROOM DISEASES |
| US6303140B1 (en) * | 1999-10-13 | 2001-10-16 | Schering-Plough Healthcare Products, Inc. | Medicated device for warts, corns, calluses and nails |
| US6585963B1 (en) * | 2001-02-15 | 2003-07-01 | Watson Pharmaceuticals, Inc. | Nail compositions and methods of administering same |
| IL160550A0 (en) * | 2001-09-04 | 2004-07-25 | Trommsdorff Arzneimittel | Plaster for the treatment of dysfunctions and disorders of nail growth |
-
2002
- 2002-09-04 IL IL16055002A patent/IL160550A0/en unknown
- 2002-09-04 RU RU2004106780/15A patent/RU2302857C2/en not_active IP Right Cessation
- 2002-09-04 PL PL367513A patent/PL205576B1/en not_active IP Right Cessation
- 2002-09-04 US US10/488,915 patent/US20040265362A1/en not_active Abandoned
- 2002-09-04 MX MXPA04001833A patent/MXPA04001833A/en active IP Right Grant
- 2002-09-04 EP EP02797674A patent/EP1423102B1/en not_active Expired - Lifetime
- 2002-09-04 KR KR1020047003255A patent/KR100757611B1/en not_active Expired - Fee Related
- 2002-09-04 PT PT02797674T patent/PT1423102E/en unknown
- 2002-09-04 NZ NZ531406A patent/NZ531406A/en not_active IP Right Cessation
- 2002-09-04 WO PCT/EP2002/009912 patent/WO2003020250A1/en active IP Right Grant
- 2002-09-04 JP JP2003524559A patent/JP4806162B2/en not_active Expired - Fee Related
- 2002-09-04 AU AU2002361825A patent/AU2002361825B2/en not_active Ceased
- 2002-09-04 CN CNA028209060A patent/CN1703206A/en active Pending
- 2002-09-04 DK DK02797674T patent/DK1423102T3/en active
- 2002-09-04 ES ES02797674T patent/ES2299630T3/en not_active Expired - Lifetime
- 2002-09-04 BR BR0212304-5A patent/BR0212304A/en not_active IP Right Cessation
- 2002-09-04 CZ CZ20040317A patent/CZ301310B6/en not_active IP Right Cessation
- 2002-09-04 CA CA002459483A patent/CA2459483C/en not_active Expired - Fee Related
- 2002-09-04 DE DE60223694T patent/DE60223694T2/en not_active Expired - Lifetime
-
2004
- 2004-02-23 ZA ZA200401445A patent/ZA200401445B/en unknown
- 2004-02-24 IL IL160550A patent/IL160550A/en not_active IP Right Cessation
- 2004-03-03 NO NO20040936A patent/NO20040936L/en not_active Application Discontinuation
-
2008
- 2008-02-15 CY CY20081100191T patent/CY1107284T1/en unknown
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