Formulation and method for the treatment of fungal nail infections

Abstract

The present invention relates to a formulation and method for the treatment of fungal nail infections, such as those caused by Trichophyton rubrum and/or Aspergillus niger . The formulation of the invention comprises glucose oxidase, D-glucose and hydrogen peroxide in an aqueous solution. Advantageously, the formulation of the invention provides a two-stage hydrogen peroxide release for the treatment of the fungal nail infections.

1 . A storage-stable antimicrobial formulation for the treatment of fungal nail infections, comprising;
 glucose oxidase at an activity of at least 10 U per 100 g of the formulation;   D-glucose from 20 to 85% by weight based on the weight of the total formulation;
 additional sugars selected from one or more of sucrose, fructose and/or maltose from 5 to 70% by weight based on the weight of the total formulation; 
   water from 10 to 20% by weight based on the weight of the total formulation;   with a pH from approximately 4 to 8   wherein the formulation provides a two-stage hydrogen peroxide release in which
 (a) storage-stable endogenously produced hydrogen peroxide is bioavailable within the formulation at a level of at least 10 mg per litre for immediate release; and 
 (b) sustained release of further hydrogen peroxide for at least a twenty-four hour period occurs upon rehydration of the formulation. 
   
   
   
       2 . A storage-stable antimicrobial formulation for the treatment of fungal nail infections, wherein the formulation has antifungal and sporocidal effects which penetrate into and through the nail plate. 
   
   
       3 . The formulation as claimed in  claim 1  for the treatment of fungal nail infections caused by  Trichophyton rubrum  and/or  Aspergillus niger.    
   
   
       4 . The formulation as claimed in  claim 1  in a form suitable for topical administration. 
   
   
       5 . The formulation as claimed in  claim 1  wherein the storage-stable endogenously produced hydrogen peroxide is bioavailable within the system at a level of at least 75 mg per litre for immediate release. 
   
   
       6 . The formulation as claimed in  claim 1  wherein the level of sustained release hydrogen peroxide produced upon rehydration of the system is at least 10 mg per litre, preferably 20 mg per litre. 
   
   
       7 . The formulation as claimed in  claim 1  further comprising a buffering agent, preferably carbonic acid-bicarbonate and/or phosphoric acid/disodium hydrogen phosphate. 
   
   
       8 . The formulation as claimed in  claim 1  wherein the additional sugars are present from 10 to 70% by weight based on the weight of the total system. 
   
   
       9 . The formulation as claimed in  claim 1  wherein the additional sugars are sucrose, fructose and maltose. 
   
   
       10 . The formulation as claimed in  claim 1  wherein fructose is present from 8 to 50% w/w %, maltose is present from 4 to 15 w/w %, sucrose is present from 0.5 to 3 w/w % and the D-glucose, is present from 10 to 85 w/w %. 
   
   
       11 . The formulation as claimed in  claim 1  further comprising at least one viscosity modifying ingredient. 
   
   
       12 . The formulation as claimed in  claim 1  adapted for delivery as part of a tissue, bandage and/or dressing. 
   
   
       13 . A combined therapy for the treatment of fungal nail infections comprising (i) the formulation of  claim 1  and (ii) an antimicrobial agent for the treatment of fungal nail infections. 
   
   
       14 . The combined therapy according to  claim 13  wherein the antimicrobial agents is selected from one or more of Griseofulvin (Grisovin®), Ketoconazole (Nizoral®), Itraconazole (Sporanox®), Terbinafine (Lamisil®), Clotrimazole, Amorolfine (Loceryl®) and/or Ciclopirox (Penlac®). 
   
   
       15 . A method for the treatment of fungal nail infections comprising the topical administration to an affected nail, or to an affected nail and surrounding skin of an effective amount of the formulation as claimed in  claim 1 . 
   
   
       16 . The method according to  claim 15  wherein the formulation penetrates into and through the nail plate. 
   
   
       17 . The method according to  claim 15  for the treatment of fungal nail infections caused by  T. rubrum  and  A. niger.    
   
   
       18 . The method according to  claim 15  wherein the formulation acts as a sporocide.