Hydrophilic gel for topical delivery of 5-aminolevulinic acid

Abstract

The present invention relates to a pharmaceutical topical gel solution that contains 5-aminolevulinic acid (5-ALA) and an aqueous low viscous gel matrix. This invention also relates to a pharmaceutical preparation containing this composition. The formulation of this type can be used in photodynamic therapy as well as in the photodynamic detection of abnormally proliferating cells.

1 . A composition comprising
 a) 5-amino-4-oxo-pentanoic acid (5-aminolevulinic acid or 5-ALA) or the HCl salt (5-ALA-HCl) thereof as an active ingredient;   b) a first penetration enhancer selected from one or more water-miscible ether compounds; and   c) a second penetration enhancer selected from one or more glycosaminoglycan compounds.   
     
     
         2 . The composition of  claim 1 , where the active ingredient is 5-aminolevulinic acid in its hydrochloride salt form (5-ALA HCl), and is contained in the composition in a concentration range of 5-30% (w/w), more preferably 10-25% (w/w) based on the overall weight of the composition. 
     
     
         3 . The composition of  claim 1 , which is a pharmaceutical composition and comprises one or more pharmaceutically acceptable auxiliaries, and preferably is a topical composition in form of a low viscous hydrogel. 
     
     
         4 . The composition of  claim 3 , where the low viscous hydrogel has a viscosity of about 1,000-13,000 mPas at 32° C. 
     
     
         5 . The composition  claim 1 , wherein the one or more non-ethoxylated water-miscible ether compounds are selected from isosorbide based compounds, preferably 1,4:3,6-dianhydrosorbitol 2,5-pentylethylether (pentylethyl isosorbide), 1,4:3,6-dianhydrosorbitol 2,5-laurylglycerylether (laurylglyceryl isosorbide) and 1,4:3,6-dianhydrosorbitol 2,5-dimethylether (dimethyl isosorbide). 
     
     
         6 . The composition of  claim 1 , wherein the one or more water-miscible ether compounds are contained in the composition in a concentration range of 4 −15% (w/w), more preferably in the range of 8-12% (w/w) based on the overall weight of the composition. 
     
     
         7 . The composition of  claim 1 , wherein the one or more glycosaminoglycan compounds are selected from chondroitin sulfate, keratan sulfate, dermatan sulfate, heparin sulfate, heparan sulfate and/or hyaluronic acid/sodium hyaluronate (non-sulfated glycosaminoglycan). 
     
     
         8 . The composition of  claim 7 , wherein the one or more glycosaminoglycan compounds are contained in the composition in a concentration range of 0.5-1.5% (w/w), more preferably in the range of 0.8-1.2% (w/w) based on the overall weight of the composition. 
     
     
         9 . The composition of  claim 1 , which is low viscous hydrogel and contains 5-ALA HCl, dimethyl isosorbide and sodium hyaluronate. 
     
     
         10 . The composition of  claim 9 , containing 5-ALA HCl in an amount of about 20% (w/w), dimethyl isosorbide in an amount of about 10% (w/w) and sodium hyaluronate in an amount of about 1% (w/w). 
     
     
         11 . The composition of  claim 1 , which further comprises one or more preservatives, chelating agents and/or buffering agents/acidity regulators. 
     
     
         12 . A method for photochemotherapeutic treatment or diagnosis of disorders or abnormalities of internal or external surfaces of the body, comprising administering or applying the composition of  claim 1 . 
     
     
         13 . The method of  claim 12 , wherein the disorders or abnormalities of internal or external surfaces of the body are selected from pre-cancer and cancers, pre-cancerous lesions of the skin such as Actinic Keratosis and other types of non-melanoma skin cancer, SCC (squamous cell carcinoma), or BCC (basal cell carcinoma). 
     
     
         14 . The composition of  claim 1 , where the one or more water-miscible ether compounds are non-ethoxylated water-miscible ether compounds.