Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-12-19
2002-08-27
Powers, Flona T. (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C548S247000
Reexamination Certificate
active
06441014
ABSTRACT:
FIELD OF THE INVENTION
This invention is in the field of antiinflammatory pharmaceutical agents and specifically relates to a crystalline form of 4-[5-methyl-3-phenylisoxazol-4-yl]benzenesulfonamide, methods of preparing the crystalline form, pharmaceutical compositions and methods for treating cyclooxygenase-2 (COX-2) associated disorders, including inflammation.
BACKGROUND OF THE INVENTION
Prostaglandins play a major role in the inflammation process and the inhibition of prostaglandin production, especially production of PGG
2
, PGH
2
and PGE
2
, has been a common target of antiinflammatory drug discovery. However, common non-steroidal antiinflammatory drugs (NSAIDs) that are active in reducing the prostaglandin-induced pain and swelling associated with the inflammation process are also active in affecting other prostaglandin-regulated processes not associated with the inflammation process. Thus, use of high doses of most common NSAIDs can produce severe side effects, including life threatening ulcers, that limit their therapeutic potential. An alternative to NSAIDs is the use of corticosteroids, which have even more drastic side effects, especially when long term therapy is involved.
Previous NSAIDs have been found to prevent the production of prostaglandins by inhibiting enzymes in the human arachidonic acid/prostaglandin pathway, including the enzyme cyclooxygenase (COX). The recent discovery of an inducible enzyme associated with inflammation (named “cyclooxygenase-2 (COX-2)” or “prostaglandin G/H synthase II”) provides a viable target of inhibition which more effectively reduces inflammation and produces fewer and less drastic side effects related to inhibition of cyclooxygenase-1 (COX-1).
A group of substituted isoxazoles are described in U.S. Pat. No. 5,633,272, to Talley et al., and International Application WO96/25405. The compounds are described to be useful for the treatment of inflammation and inflammation-associated disorders. 4-[5-Methyl-3-phenylisoxazol-4-yl]benzenesulfonamide shows potential as a selective inhibitor of COX-2 over COX-1.
With all pharmaceutical compounds and compositions, the chemical and physical stability of a drug compound is important in the commercial development of that drug substance. Such stability includes the stability at ambient conditions, especially to moisture and under storage conditions. Elevated stability at different conditions of storage is needed to anticipate the different possible storage conditions during the lifetime of a commercial product. A stable drug avoids the use of special storage conditions as well as frequent inventory replacement. A drug compound must also be stable during the manufacturing process which often requires milling of the drug to achieve drug material with uniform particle size and surface area. Unstable materials often undergo polymorphic changes. Therefore, any modification of a drug substance which enhances its stability profile provides a meaningful benefit over less stable substances.
It has now been discovered that 4-[5-methyl-3-phenylisoxazol-4-yl]benzenesulfonamide can be prepared in different crystal forms. An earlier material (Form “A”) is unstable after mechanical grinding (milling) and is also thermally unstable. A recently determined crystalline form (Form “B”) is described which is more stable and has improved physical properties.
REFERENCES:
patent: 5633272 (1997-05-01), Talley et al.
patent: 5643933 (1997-07-01), Talley et al.
patent: 95/00501 (1995-01-01), None
patent: 96/38442 (1996-05-01), None
Gaud Henry T
McLaughlin Kathleen T
Medich John R
Talley John J
Yonan Edward E
G.D. Searle & Co.
McDonnell & Boehnen Hulbert & Berghoff
Powers Flona T.
LandOfFree
Crystalline form of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Crystalline form of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Crystalline form of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2950561