Use of hydrophilic penetration agents in dermatological compositions for the treatment of onychomycoses, and corresponding compositions

• US 6,455,592 B1
• Filed: 10/04/2000
• Issued: 09/24/2002
• Est. Priority Date: 03/08/1991
• Status: Expired due to Term

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Touzan, Philippe, Rigenbach, François, Rude, Marie-France, Laugier, Jean-Pierre
• Primary Examiner(s): Weddington, Kevin E.
• Application Number:
  US09/678,772
• Time in Patent Office: 720 Days
• Field of Search: 514/655, 514/724
• US Class Current: 514/655
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 8/33 containing oxygen
• CPC Class Codes: A61K 8/41 Amines
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61Q 3/00 Manicure or pedicure preparations

Abstract

The hydrophilic penetration agents customarily used for the transcutaneous penetration of active ingredients are, surprisingly, found to improve the penetration of antifungal agents through the nails. A corresponding dermatological composition contains at least one antifungal agent chosen, in particular, from among those of the allylamine family, such as terbinafine-HCl and naftifine-HCl; at least one hydrophilic penetration agent chosen, in particular, from among the glycols, glycol monoethers, glycol diethers, dimethylsulphoxide, caprolactam, dimethylisosorbide, isopropylidene glycerol, dimethylimidazolidinone, ethyl lactate, the polyoxyethylenated C₈-C₁₀ glycerides, polyethylene glycol 20 glyceryl laurate and dimethylacetamide; and a water-alcohol solvent medium which dissolves the said antifungal agent(s) and in which the said penetration agent(s) is (or are) at least partially miscible.

Claims

1. A topical composition for treatment of onychomycoses of the nail comprising

a) a pharmacologically-effective amount of terbinafine hydrochloride;

b) a solvent medium comprising water and at least one straight- or branched-chain C₂-C₈ alkanol; and

c) a hydrophilic penetration agent.

2. A composition in accordance with claim 1 wherein said terbinafine hydrochloride is present in a concentration of 2 to 30% by weight relative to the total weight of said composition.

3. A composition according to claim 1 wherein said hydrophilic penetration agent is selected from the group consisting of glycols, glycol monoethers, glycol diethers, dimethylsulphoxide, caprolactam, dimethylisosorbide, isopropylidene glycerol, dimethylimidazolidinone, N-methyl-pyrrolidone-2, pyrrolidone-2, ethyl lactate, polyoxyethylenated C₈-C₁₀ glycerides, polyethylene glycol glyceryl laurate and dimethylacetamide.

4. A composition in accordance with claim 3, wherein the glycols are selected from the group consisting of propylene glycol, butylene glycol, hexylene glycol, ethylene glycol and polyethylene glycols;

the glycol monoethers are selected from the group consisting of monoethers of ethylene glycol and monoethers of propylene glycol; and

the glycol diethers are selected from the group consisting of propylene glycol dimethyl ether and dipropylene glycol dimethyl ether.

5. A composition in accordance with claim 4 wherein the penetration agent is dipropylene glycol dimethyl ether.

6. A composition in accordance with claim 1, wherein said penetration agent is present in a concentration of 1 to 60% by weight relative to the total weight of the composition.

7. A composition in accordance with claim 1, wherein the water and the C₂-C₈ alkanol are present in proportions, respectively, of 5 to 30% by weight and 10 to 90% by weight, relative to the total weight of the composition.

8. A composition in accordance with claim 1, further comprising at least one additive selected from the group consisting of preservative agents, antioxidants, colorants, charges, pigments and polymers intended to prevent running of the composition before penetration.

9. A composition in accordance with claim 1, in the form of a lotion or a fluid gel.