This invention relates to pharmaceutical compositions for the treatment of cyclooxygenase-2 mediated diseases, mehe use of a compound in the manufacture of a medicament.
In particular, this invention relates to a pharmaceutical composition for the treatment of cyclooxygenase-2 mediated diseases, said composition being suitable for once a day administration, said composition comprising a cyclooxygenase-2 inhibiting characterized by high potency for the inhibition of cyclooxygenase-2, a long half-life and a high degree of specificity for inhibiting cyclooxygenase-2 in preference to cyclooxygenase-1. Such a compound is exemplified by 3-phenyl-4-(4-methylsulfonyl)phenyl)-2-(5H)-furanone, ##STR1##
Non-steroidal anti-inflammatory agents are normally administered 2 to 4 times daily. The relatively short half-life of most non-steroidal anti-inflammatory agents means that once a day administration is impractical and even twice a day administration is unusual. The relatively large doses needed to achieve once a day treatment of conventional non-steroidal anti-inflammatory agents would also lead to side effects so that there is a general understanding that once a day administration is unlikely to be achievable.
Surprisingly a compound has been identified which can be employed on a once a day basis and which will not produce an unacceptable level of side effects on such a regimen, and in particular will not cause an unacceptable level of gastric side effects.
U.S. Pat. No. 5,474,995, issued Dec. 12, 1995, WO 95/00501, published Jan. 5, 1995 and WO 95/18799, published Jul. 13, 1995, disclose 3,4-di-substituted furanones and derivatives thereof as potent, selective inhibitors of cyclooxygenase-2. We have found that 3-phenyl-4-(4-methylsulfonyl)phenyl)-2-(5H)-furanone, possesses a surprising combination of attributes that make it possible to formulate and use the composition in a surprising manner. Not only is the compound potent, safe and effective at modest oral dosages of 5 to 125 mg of agent per day, but in addition this active agent possesses a half-life in humans of sufficient length that a single oral dose of 5 to 125 mg of agent per day will provide effective safe anti-inflammatory treatment over a 24 hour period. Such active agents are particularly useful in the treatment of chronic indications, including arthritis, pain, Alzheimer's disease and the like.
USPTO Backgrounds
USPTO Backgrounds