Hydrophilic gel for topical delivery of 5-aminolevulinic acid
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) 4-15% (w/w) of a first penetration enhancer selected from one or more non-ethoxylated water-miscible ether compounds selected from: 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); and
c) 0.5-0.15% (w/w) of a second penetration enhancer from a glycosaminoglycan compound: sodium hyaluronate.
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) 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.
4. The composition of claim 3 , which is a topical composition in form of a low viscous hydrogel, where the low viscous hydrogel has a viscosity of about 1,000-13,000 mPas at 32° C.
5. The composition of claim 1 , which is low viscous hydrogel and contains 5-ALA HCl, dimethyl isosorbide and sodium hyaluronate.
6. The composition of claim 5 , 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).
7. The composition of claim 1 , which further comprises one or more preservatives, chelating agents and/or buffering agents/acidity regulators.
8. 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 .
9. The method of claim 8 , 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 and other types of non-melanoma skin cancer, SCC (squamous cell carcinoma), or BCC (basal cell carcinoma).
10. 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 10-25% (w/w) based on the overall weight of the composition.
11. The composition of claim 3 , which is a topical composition in form of a low viscous hydrogel.
12. The composition of claim 1 , wherein the one or more non-ethoxylated water-miscible ether compounds are contained in the composition in a concentration range of 8-12% (w/w) based on the overall weight of the composition.
13. The composition of claim 1 , wherein the glycosaminoglycan compound: sodium hyaluronate is contained in the composition in a concentration range of 0.8-1.2% (w/w) based on the overall weight of the composition.
14. The method of claim 8 , wherein the disorders or abnormalities of internal or external surfaces of the body are pre-cancerous lesions of the skin being Actinic Keratosis.
15. The composition of claim 5 , wherein the dimethyl isosorbide is in an amount of about 10% (w/w) or more.