5-ala literature
There are a lot of papers on the use of 5-ala (or derivatives) for a whole range of cancers, inclusing melanoma, bronchial tumors, esophegal cancer, prostate cancer, etc.
This paper deals with derivatives of 5-ala, which require much lower doses:
Vena FC, Turchiello RF, Laville I, Pigaglio S, Blais J, Tedesco AC. 5-Aminolevulinic acid ester-induced protoporphyrin IX in a murine melanoma cell line. Lasers Med Sci. 2004 Aug 31
Departamento de Quimica, FFCLRP, Universidade de Sao Paulo, Av. dos Bandeirantes 3900, 14040-901, Ribeirao Preto, Sao Paulo, Brazil.
The use of 5-aminolevulinic acid (5-ALA) ester derivatives as precursors of endogenous protoporphyrin IX (PpIX) has been proposed as a good strategy for improved drug diffusion across biological membranes. In the present work, the 5-ALA ester derivatives hexyl-ALA (h-ALA), octyl-ALA (o-ALA), and decyl-ALA (d-ALA) were synthesized, and their efficacy to induce endogenous PpIX was explored in a murine melanoma cell line (B-16) as compared with that of 5-ALA. The maximum level of PpIX induced in cells treated with 5-ALA, h-ALA, o-ALA, and d-ALA was reached at optimal concentrations of 0.3, 0.075, 0.1, and 0.075 mM, respectively. The derivatives h-ALA and o-ALA appear as the most efficient PpIX precursors in this cell line, since a higher or similar PpIX production could be achieved with a fourfold and threefold lower dose of these precursors compared with 5-ALA. The phototoxicity effect of h-ALA and o-ALA ester derivatives showed the same phototoxicity behavior detected for 5-ALA but at much lower drug doses. Our study suggests that h-ALA and o-ALA esters improve intracellular PpIX formation in B-16 cells at reduced concentrations. This should enable clinical applications at lower precursor doses with reduced effective costs.
I checked the ASAT 5-ala patent to see whether 5-ala derivatives were covered:
United States Patent: 6,559,183
Date: May 6, 2003
Assignee: ASAT AG Applied Science & Technology (Zug, CH)
Title: Nano-emulsion of 5-aminolevulinic acid
The present invention relates to nanoemulsions which contain 5-aminolevulinic acid or its derivatives, precursors or metabolites.
Looks like this is covered.
