Use of aminolevulinic acid and derivatives thereof

Abstract

The invention provides the use of a photosensitiser which is a derivative (e.g. an ester) of 5-aminolevulinic acid (5-ALA), or a pharmaceutically acceptable salt thereof, in the manufacture of a composition for use in methods of photodynamic therapy (PDT) on an animal, wherein said PDT comprises: (a) administering to said animal a composition comprising said photosensitiser; and (b) photoactivating said photosensitiser, and side-effects (e.g. pain and/or erythema) of said PDT are prevented or reduced by use of one or more of (i)-(iv): (i) said composition comprises said photosensitiser in a concentration of less than 10% wt (e.g. 0.5 to 8% wt), (ii) said composition is administered for less than 2 hours (e.g. 30 minutes to 90 minutes) prior to said photoactivation, (iii) said photoactivation is carried out with a light source having a fluence rate of less than 50 mW/cm 2 (e.g. 5 to 40 mW/cm 2 ), (iv) said photoactivation is carried out with sunlight. Preferably, side effects of PDT are prevented or reduced by using (ii) or (iv) in combination with (i) and/or (ii).

1 . A method of photodynamic treatment of acne comprising:
 (a) administering to an area characterized by acne on a patient in need of such treatment a composition comprising methyl ALA ester at a concentration of 4% to less than 10% by weight of the composition, or the equivalent concentration of a pharmaceutically acceptable salt, for a period of 30 minutes to less than 2 hours, and   (b) administering photoactivating light to the area.   
     
     
         2 . The method of  claim 1 , wherein the concentration of methyl ALA ester is 4 to 8% by weight of the composition, or the equivalent concentration of a pharmaceutically acceptable salt. 
     
     
         3 . The method of  claim 1 , wherein the concentration of methyl ALA ester is 8% by weight of the composition, or the equivalent concentration of a pharmaceutically acceptable salt. 
     
     
         4 . The method of  claim 1 , wherein the administered compound is methyl ALA ester hydrochloride salt. 
     
     
         5 . The method of  claim 4 , wherein the composition is administered for a period of 30 to 90 minutes. 
     
     
         6 . The method of  claim 1 , wherein the composition is administered for a period of 90 minutes. 
     
     
         7 . The method of  claim 1 , wherein the concentration of methyl ALA ester is 8% by weight of the composition, or the equivalent concentration of a pharmaceutically acceptable salt and the composition is administered for a period of 90 minutes. 
     
     
         8 . The method of  claim 7 , wherein the administered compound is methyl ALA ester hydrochloride salt. 
     
     
         9 . The method of  claim 1 , wherein the composition is a cream. 
     
     
         10 . The method of  claim 8 , wherein the composition is a cream 
     
     
         11 . The method of  claim 1 , wherein the photoactivating light has a peak wavelength in the range 631 to 637 nm. 
     
     
         12 . The method of  claim 1 , wherein the total light dosage is about 37 J/cm 2 . 
     
     
         13 . The method of  claim 12 , wherein the photoactivating light has a fluence rate of about 68 mW/cm 2 . 
     
     
         14 . The method of  claim 12 , wherein the photoactivating light has a fluence rate of less than 50 mW/cm 2 . 
     
     
         15 . The method of  claim 12 , wherein the photoactivating light has a fluence rate of about 46 mW/cm 2 . 
     
     
         16 . The method of  claim 1 , wherein the photoactivating light is provided by an LED lamp. 
     
     
         17 . The method of  claim 8 , wherein the photoactivating light has a peak wavelength in the range 631 to 637 nm. 
     
     
         18 . The method of  claim 8 , wherein the total light dosage is about 37 J/cm 2 . 
     
     
         19 . The method of  claim 18 , wherein the photoactivating light has a fluence rate of about 68 mW/cm 2 . 
     
     
         20 . The method of  claim 18 , wherein the photoactivating light has a fluence rate of about 46 mW/cm 2 . 
     
     
         21 . The method of  claim 8 , wherein the photoactivating light is provided by an LED lamp. 
     
     
         22 . The method of  claim 1 , wherein the photoactivating light is provided by an LED lamp, has a peak wavelength in the range 631 to 637 nm, has a fluence rate of about 68 mW/cm 2  or 46 mW/cm 2  and the total light dose is about 37 J/cm 2 . 
     
     
         23 . The method of  claim 8 , wherein the photoactivating light is provided by an LED lamp, has a peak wavelength in the range 631 to 637 nm, has a fluence rate of about 68 mW/cm 2  or 46 mW/cm 2  and the total light dose is about 37 J/cm 2 . 
     
     
         24 . The method of  claim 1 , wherein acne is inflammatory acne. 
     
     
         25 . The method of  claim 1 , wherein acne is acne vulgaris. 
     
     
         26 . The method of  claim 1 , wherein acne is severe to moderate acne. 
     
     
         27 . The method of  claim 8 , wherein acne is severe to moderate acne. 
     
     
         29 . The method of  claim 1 , wherein the composition is removed prior to administering photoactivating light to the affected area. 
     
     
         30 . The method of  claim 1 , wherein the composition is administered under occlusion.