2005 年 25 巻 6 号 p. 512-516
TA-270 is a novel compound that demonstrates 5-lipoxygenase (LO) inhibition and anti-oxidative action against ONOO- etc. TA-270 was designed on the basis of the ascorbic acid and aspirin, and added with sinapinic acid (an active ingredient of SAIBOKUTOU). Here, we investigated the effects of TA-270 on inflammatory airway diseases using experimental guinea pig models.
In a pre-clinical study, TA-270 strongly improved biphasic asthmatic responses and hyperresponsiveness in allergic asthma models, hyperresponsiveness induced by ozone inhalation in non-allergic models and also biphasic nasal blockages in allergic rhinitis models. The inhibitory effect of TA-270 against the hyperresponsiveness in allergic models was remarkably stronger than that of a cysteinyl leukotriene antagonist, suggesting that the anti-oxidative action rather than 5-LO inhibitory effect contributes to the inhibitory effect of TA-270. It is recently reported that a potent oxidant ONOO- generated from nitric oxide and O2- is involved in the development of respiratory diseases. And our study showed that TA-270 inhibited hyperresponsiveness induced by ONOO- in guinea pigs. These results suggest that the anti-oxidative action of TA-270 is involved in the improvement of airway inflammation.
In conclusion, TA-270 is considered to improve airway inflammation through its mechanism of 5-LO inhibitory and anti-oxidative effect, and is expected clinically to demonstrate improvement in airway inflammation including asthma and chronic obstructive pulmonary disease, and allergic rhinitis.