Use of aminolevulinic acid and derivatives thereof
The invention provides the use of a photosensitizer which is 5-aminolevulinic acid (5-ALA) or a derivative (e.g. an ester) of 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 photosensitizer; and (b) photoactivating said photosensitizer, and wherein 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 photosensitizer 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 (iii) or (iv) in combination with (i) and/or (ii).
1. A method of treating pre-malignant and malignant abnormalities and disorders of at least one of a lining of the vagina, cervix or uterus in an animal by photodynamic therapy (PDT), wherein said PDT comprises:
(a) administering to said animal a composition comprising an ester of 5-aminolevulinic acid (5-ALA) or a pharmaceutically acceptable salt thereof, as a photosensitiser; and
(b) photoactivating said photosensitiser,
and wherein side-effects of said PDT are prevented or reduced by use of (i) in combination with (ii):
(i) said composition comprises said photosensitiser in a concentration of less than 10% wt,
(ii) said photoactivation is carried out with a light source comprising a light emitting diode and having a fluence rate of less than 50 mW/cm 2 .
2. The method of claim 1 , wherein said PDT has substantially the same therapeutic effect as the corresponding standard PDT treatment.
3. The method of claim 1 , 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 a substituted or unsubstituted, straight-chained, branched or cyclic alkyl group; and each R 2 independently represents a hydrogen atom) or a pharmaceutically acceptable salt thereof.
4. The method of claim 3 , wherein in formula I, R 1 represents an unsubstituted alkyl group or an alkyl group substituted by an aryl group.
5. The method of claim 1 , wherein said composition further comprises a second photosensitiser.
6. The method of claim 1 , wherein the photosensitizer is hexyl ALA ester (HAL) or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , wherein the photosensitizer is the hydrochloric acid salt of hexyl ALA ester (HAL).
8. The method of claim 1 , wherein the abnormality or disorder is pre-malignant.
9. The method of claim 8 , wherein the abnormality or disorder is a pre-malignant lesion of the cervix.
10. The method of claim 9 , wherein the abnormality or disorder is a viral infection.
11. The method of claim 9 , wherein the photosensitizer is hexyl ALA ester (HAL) or a pharmaceutically acceptable salt thereof.
12. The method of claim 11 , wherein the photosensitizer is the hydrochloric acid salt of hexyl ALA ester (HAL).
13. The method of claim 12 , wherein the photosensitizer is present in the composition at a concentration of 0.05 percent to 8 percent by weight.
14. The method of claim 13 , wherein the photosensitizer is present in the composition at a concentration of 2 percent to 8 percent by weight.
15. The method of claim 1 , wherein the fluence rate is 5 to 40 mW/cm 2 .
16. The method of claim 1 , wherein the animal is a human and the lining is the lining of the cervix.