Treatment of Acne Using Derivatives of 5-Aminolevulinic Acid

Abstract

The invention provides 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 medicament for use in the prevention or treatment of acne.

1 . A method of preventing or treating acne comprising administering to an area of skin on a body a photosensitiser which is a derivative of 5-aminolevulinic acid (5-ALA), or a pharmaceutically acceptable salt thereof, and photoactivating said photosensitiser, wherein said photosensitiser is a compound of general formula I:
   R 2   2 N—CH 2 COCH 2 —CH 2 CO—OR 1    (I)   (wherein   R 1  represents an unsubstituted alkyl group or an alkyl group substituted by an aryl group; and each R 2  independently represents a hydrogen atom or an optionally substituted alkyl group).   
     
     
         2 . The method of  claim 1 , wherein in formula I each R 2  represents a hydrogen atom. 
     
     
         3 . The method of  claim 1 , wherein in formula  1 , R 1  represents a C 1-2  alkyl group optionally substituted by an aryl group. 
     
     
         4 . The method of  claim 3 , wherein said compound is selected from methyl ALA ester, benzyl ALA ester or substituted benzyl ALA ester. 
     
     
         5 . The method of  claim 1 , wherein in formula  1 , R 1  represents an alkyl group substituted by an aryl group. 
     
     
         6 . The method of  claim 1 , wherein in formula  1 , R 1  represents an aryl substituted C 1-4  alkyl group wherein said aryl group is itself optionally substituted, and each R 2  is as defined in  claim 1 . 
     
     
         7 . The method of  claim 6 , wherein said compound is selected from the group consisting of benzyl ALA ester, 4-isopropylbenzyl ALA ester, 4-methylbenzyl ALA ester, 2-methylbenzyl ALA ester, 3-methylbenzyl ALA ester, 4-[t-butyl]benzyl ALA ester, 4-[trifluoromethyl]benzyl ALA ester, 4-methoxybenzyl ALA ester, 3,4-[di-chloro]benzyl ALA ester, 4-chlorobenzyl ALA ester, 4-fluorobenzyl ALA ester, 2-fluorobenzyl ALA ester, 3-fluorobenzyl ALA ester, 2,3,4,5,6-pentafluorobenzyl ALA ester, 3-nitrobenzyl ALA ester, 4-nitrobenzyl ALA ester, 2-phenylethyl ALA ester, 4-phenylbutyl ALA ester, 3-pyridinyl-methyl ALA ester, 4-diphenyl-methyl ALA ester and benzyl-5-[(1-acetyloxyethoxy)-carbonyl]amino levulinate. 
     
     
         8 . The method of  claim 5 , wherein said compound is selected from benzyl ALA ester or substituted benzyl ALA ester. 
     
     
         9 . The method of  claim 1 , wherein in formula  1 , R 1  represents an unsubstituted alkyl group. 
     
     
         10 . The method of  claim 9 , wherein said compound is selected from methyl ALA ester, ethyl ALA ester, propyl ALA ester, butyl ALA ester, pentyl ALA ester, hexyl ALA ester, octyl ALA ester, 2-methylpentyl ALA ester, 4-methylpentyl ALA ester, 1-ethylbutyl ALA ester, 3,3-dimethyl-1-butyl ALA ester. 
     
     
         11 . The method of  claim 9 , wherein said compound is selected from methyl ALA ester, hexyl ALA ester and 4-methylpentyl ALA ester. 
     
     
         12 . The method of  claim 1 , wherein said acne is associated with  Propionibacterium acnes, Propionibacterium avidum  or  Propionibacterium granulosum.    
     
     
         13 . The method of  claim 1 , wherein said acne is selected from acne vulgaris, acne rosacea, acne conglobate, acne papulosa and premenstrual acne. 
     
     
         14 . The method of  claim 1 , wherein the photosensitiser is administered together with a second photosensitiser, and the photosensitisers are photoactivated. 
     
     
         15 . A kit or pack containing a photosensitiser as defined in  claim 1 , or a pharmaceutically acceptable salt thereof, and separately a second photosensitiser for simultaneous, separate or sequential use in a method of treating or preventing acne. 
     
     
         16 . The method of  claim 1 , wherein the photosensitiser, or a pharmaceutically acceptable salt thereof, is administered together with at least one surface-penetration assisting agent, and optionally one or more chelating agents. 
     
     
         17 . The method of  claim 1 , wherein the photosensitiser, or a pharmaceutically acceptable salt thereof, is administered together with a non-photosensitising acne treatment agent. 
     
     
         18 . A product or kit for use in a method of treating or preventing acne comprising:
 (a) a first container containing a photosensitiser as defined in  claim 1 , or a pharmaceutically acceptable salt thereof; and   (b) a second container containing a non-photosensitising acne treatment agent.   
     
     
         19 . The method of  claim 1 , wherein the method is the cosmetic treatment of acne. 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 1 , optionally entailing the step of waiting for a time period necessary for the photosensitiser to achieve an effective tissue concentration at the desired site prior to photoactivating the photosensitiser at the desired site. 
     
     
         22 . The method of  claim 1 , wherein R 1  represents an unsubstituted C 1-8  alkyl. 
     
     
         23 . The method of  claim 1 , wherein R 1  represents a C 1-2  alkyl substituted by an aryl group. 
     
     
         24 . The method of  claim 3 , wherein R 1  represents a C 1  alkyl group optionally substituted by an aryl group. 
     
     
         25 . The method of  claim 5 , wherein R 1  represents C 1  or C 2  alkyl substituted by a phenyl group. 
     
     
         26 . The method of  claim 6 , wherein R 1  represents an aryl substituted C 1  or C 2  alkyl group, wherein said aryl group comprises up to 20 carbon atoms, and each R 2  is hydrogen. 
     
     
         27 . The method of  claim 8 , wherein said compound is selected from benzyl ALA ester, 4-nitrobenzyl ALA ester, and 4-chlorobenzyl ALA ester. 
     
     
         28 . The method of  claim 9 , wherein in formula  1 , R 1  represents an unsubstituted C 1-8  alkyl. 
     
     
         29 . The method of  claim 11 , wherein said compound is methyl ALA ester. 
     
     
         30 . The method of  claim 13 , wherein said acne is acne vulgaris. 
     
     
         31 . The method of  claim 19 , wherein the acne is on the face.