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R. Herrero-Vanrell, V. Andres, I. T. Molina-Martinez, P. Alarma-Estrany, A. Peral, J. Pintor; Hyaluronic Acid Enhances the Ocular Hypotensive Effect of a Melatonin Analogue (5-MCA-NAT). Invest. Ophthalmol. Vis. Sci. 2007;48(13):3933.
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Topical application of 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT), a selective MT3 melatonin receptor agonist, produces a clear reduction in intraocular pressure. This active substance has been vehiculized in mixtures of propylene-glycol (PG) and isotonic phosphate buffer solution (PBS).Hyaluronic acid (HA) is a mucoadhesive polymer able to adhere to mucins increasing the ocular surface contact time of formulations.The aim of this work was to prepare new ophthalmic preparations of 5-MCA-NAT dissolved in mixtures of PG:PBS and evaluate the addition of hyaluronic acid in the hypotensive effect of the active substance after instillation in rabbit eyes.
5-MCA-NAT (Tocris Bioscience, Missouri, USA), 1,2 propylene-glycol (PG) (Guinama, Barcelona, Spain) and Hyaluronic Sodium Salt (HA-Na) Ophthalmic grade (Mw 400.000 Da) (Materias primas Abaran, Madrid, Spain). Formulations including 5-MCA-NAT (Doses 100 µM and 500µM) were prepared with different vehicles: PG:PBS (10:90 and 50:50). Solutions including hyaluronic acid sodium salt contained the mucoadhesive polymer at 0.2%. Male New Zealand white rabbits (2.5-3Kg) were used for the in-vivo studies. 10 µl of each formulation was instilled in the cul the sac of the right eye. The left eye received the same volume of vehicle. Two measurements of the intraocular pressure (PIO) were taken before any compound was administered. Then, PIO evaluations were carried out 1,2,3,4,5,6,7 and 8 hours after administration. Each formulation was assayed in four animals. All the in-vivo experiments were conducted in compliance with the ARVO statements for the Use of Animals in Ophthalmolgy and Vision Research.
The maximum decrease of the PIO (25%) was observed between one to three hours after instillations. IOP decreases were still maintained at the end of the assay in formulations including hyaluronic acid. No significant differences were observed between the responses observed for the different proportions of PG and PBS employed (10:90 and 50:50).
Formulations including HA-Na would be able to minimize the number of 5-MCA-NAT topical applications. Taking into account that HA-Na is well tolerated in long term therapies, it can be considered as a good vehicle for 5-MCA-NAT in chronic treatments.
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