Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1999-03-08
2000-05-16
Jarvis, William R. A.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61K 3134
Patent
active
060638117
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
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.
SUMMARY OF THE INVENTION
This invention is directed to a pharmaceutical composition for the treatment of cyclooxygenase-2 mediated diseases, said composition being suitable for once a day oral administration, said composition comprising a cyclooxygenase-2 inhibiting compound 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.
In one aspect, this invention is directed to a pharmaceutical composition for the treatment of cyclooxygenase-2 mediated diseases, aid composition being suitable for once a day oral administration, said composition comprising 5 to 125 mgs of the above mentioned compound.
The invention is also directed to a method of treating cyclooxygenase-2 mediated diseases comprising the once a day oral administration of 5 to 125 mgs of the above mentioned compound.
The invention is also directed to the use the above mentioned compound in the manufacture of a medicament containing 5 to 125 mgs of said compound for once a day administration for the treatment of cyclooxygenase-2 mediated diseases.
DETAILED DESCRIPTION OF THE INVENTION
In one embodiment, this invention is directed 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 inhibitor characterized by high potency for the inhibition of cyclooxygenase-2, a long half-life and a high degree of specificity
REFERENCES:
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Clinical Pharmacology, Mar. 30, 1999, (3) 211-231, Thierry Lave, et al.
Journal of Pharmaceutical Sciences, vol. 86, No. 5, May 1997 p p 584-590.
Journal of Pharmacology and Experimental Therapuetics, vol. 283, No. 1, pp 46-58 (1997).
Davies, B. and Morris, T., Pharmaceutical Research 10, 1093-1095 (1993), T. Physiological Parameters in Laboratory Animals and Humans.
Lin, Drug Metabolism and Disposition, vol. 23, No. 10, 1008-1021 (1995).
Iwatsubo, et al., Biopharmaceutics & Drug Disposition, vol. 17, 273-310 (1996).
Mordenti, J., Journal of Pharmaceutical Science 75, 1028-1040 (1986), Man versus Beast: Pharmacokinetic Scaling in Mammals.
Rowland and Tozer, Clinical Pharmacokinetics: Concepts and Applications (1980).
Osteoarthritis and Cartilage: vol. 5 (Suppl. A) May 1997.
Arthritis & Rheumatism, vol. 40, No. 9(Suppl.) Sep. 1997.
Ehrich Elliot
Gertz Barry
Hancock Bruno
Winters Conrad
Jarvis William R. A.
Merch Frosst Canada & Co.
Merck & Co. , Inc.
Panzer Curtis C.
Rose David L.
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