Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-02-07
2002-11-26
Criares, Theodore J. (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S406000, C514S403000, C514S730000, C514S734000
Reexamination Certificate
active
06486203
ABSTRACT:
TECHNICAL FIELD
The invention herein is directed to an expansion of the use of selective inhibitors of cyclooxygenase-2 and of natural substances which inhibit cyclooxygenase-2.
BACKGROUND OF THE INVENTION
Prostaglandins are important mediators of inflammation that are produced at elevated levels in inflamed tissues. The increased amounts of prostaglandins produced in inflamed tissues reflect enhanced synthesis, which occurs by cyclooxygenase-catalyzed metabolism of arachidonic acid. Two different isoforms of cyclooxygenase (COX) designated cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) have been identified. COX-1 is a constitutive isoform present in most tissues. COX-2 is not detectable in most normal tissues, but it is induced by cytokines, growth factors, oncogenes and tumor promoters. The increased production of prostaglandins in the joints of patients with rheumatoid arthritis has been attributed to elevated levels of COX-2.
Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin inhibit the activities of COX-1 and COX-2 and therefore the synthesis of pro-inflammatory prostaglandins. NSAID-mediated inhibition of COX-1 is believed to be responsible for side effects such as peptic ulcer disease. Selective inhibitors of COX-2 have been developed in an effort to decrease the side effects of traditional NSAIDs. In fact, selective inhibitors of COX-2 do appear to be very effective inhibitors of rheumatoid arthritis while causing fewer gastrointestinal side effects than traditional NSAIDs.
While aspirin has been used to treat sore throat, heretofore there has been no proof that COX-2 is upregulated in sore throat and no suggestion of the use of selective inhibitors of COX-2 or of use of COX-2 inhibitors from natural sources, to treat sore throat.
While nitric oxide synthase inhibitors have been suggested for treating acute and chronic inflammatory diseases including sinusitis (see Williamson et al. U.S. Pat. No. 5,710,181), heretofore there has been no description of the use of selective inhibitors of COX-2 or of the use of COX-2 inhibitors from natural sources, to treat sinusitis.
SUMMARY OF THE INVENTION
The invention herein is directed to a method for treating a patient with an inflammatory disease of the head and neck comprising administering to said patient a therapeutic amount of a selective inhibitor of cyclooxygenase-2 or of a cyclooxygenase-2 inhibitor from a natural source.
The term “inflammatory disease of the head and neck” includes, without limitation, sore throat, e.g., that caused by tonsillitis or pharyngitis, and sinusitis.
The term “tonsillitis” is used herein to mean an acute inflammation of the palatine tonsils and includes tonsillitis caused by bacterial and viral infections.
The term “pharyngitis” is used herein to mean an acute inflammation of the pharynx and includes pharyngitis caused by bacterial and viral infections.
The term “sinusitis” is used herein to mean an inflammatory process in the paranasal sinuses and includes such condition caused by viral, bacterial and fungal infections or allergic reactions.
The term “inhibitor of cyclooxygenase-2” is used herein to mean a compound which directly inhibits cyclooxygenase-2 metabolized catalysis of arachidonic acid and/or inhibits the transcription of cyclooxygenase-2 and excludes nitric oxide synthase inhibitors. The term includes competitive inhibitors as well as non-competitive inhibitors.
The term “selective inhibitor of cyclooxygenase-2” is used herein to mean compound which selectively inhibits cyclooxygenase-2 in preference to cyclooxygenase-1 and particularly compound for which the ratio of the IC
50
concentration (concentration inhibiting 50% of activity) for cyclooxygenase-1 to the IC
50
concentration for cyclooxygenase-2 is greater than 1. Such ratio is readily determined by assaying for cyclooxygenase-2 activity and assaying for cyclooxygenase-1 activity by the methods set forth at column 39, line 55—column 40, line 36 of Talley et al. U.S. Pat. No. 5,633,272, which is incorporated herein by reference, and from the resulting data obtaining a ratio of IC
50
s.
The term “natural source” in the phrase “cyclooxygenase-2 inhibitor from a natural source” is a plant, marine or animal organism.
DETAILED DESCRIPTION
We turn firstly to the selective inhibitors of cyclooxygenase-2. The selective inhibitors of cyclooxygenase-2 are synthetic compounds.
The selective inhibitors of cyclooxygenase-2 are preferably those where the ratio of the IC
50
concentration for cyclooxygenase-1 to the IC
50
concentration for cyclooxygenase-2 is 100 or more.
Selective inhibitors of cyclooxygenase-2 include the following compounds:
(1) 4-[5-(4-Chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(2) 4-[5-(4-Bromophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(3) 4-[5-(3-Chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(4) 4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(5) 4-[5-(2-Chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(6) 4-[5-(4-Trifluoromethylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(7) 4-[5-(4-Fluorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(8) 4-[5-Phenyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(9) 4-[5-(4-Methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(10) 4-[5-(4-Trifluoromethoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(11) 4-[5-(2-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(12) 4-[5-(4-Chlorophenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(13) 4-[4-(Aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazol-3-carboxylate
(14) 4-[4-(Aminosulfonyl)phenyl]-5-(4-chlorophenyl)-1H-pyrazol-3-carboxamide
(15) 4-[5-(4-[Methylthio]phenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(16) 4-[5-(4-[Methylsulfonyl]phenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(17) 4-[5-(2,4-[Difluoro]phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(18) 4-[5-(2,6-[Difluoro]phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(19) 4-[5-(4-Cyanophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(20) 4-[5-(4-Chlorophenyl)-3-(heptafluoropropyl)-1H-pyrazol-1-yl]benzenesulfonamide
(21) 4-[5-(4-Chlorophenyl)-3-(chloro-difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(22) 4-[5-(4-Chlorophenyl)-3-(pentafluoroethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(23) 4-[5-(4-Biphenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(24) 4-[5-(4-Pyrazinyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(25) 4-[5-(5-Chloro-2-thienyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(26) 4-[5-(4-Morpholino)phenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(27) 4-[5-(1-Cyclohexyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(28) 4-[5-(5-Bromo-2-thienyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(29) 4-[5-(4-Thienyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(30) 4-[5-(4-[Trifluoromethyl]phenyl)-3-(difluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(31) 4-[5-(3,4-Dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(32) 4-[5-(2,4-Dichlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
(33) 4-[5-Phenyl-3-(3-hydroxypropyl)-1H-pyrazol-1-yl]benzenesulfonamide
(34) 4-[5-(4-Fluorophenyl)-3-(3-hydroxypropyl)-1H-pyrazol-1-yl]benzenesulfonamide
(35) 4-[4-(Aminosulfonyl)phenyl]-5-(4-fluorophenyl)-1H-pyrazole]-3-propanoic acid
(36) 4,5-Dihydro-4-[3-trifluoromethyl]-1H-benz[g]indazol-1-yl]benzenesulfonamide
(37) 4-[5-(4-Chloroph
Cornell Research Foundation Inc.
Criares Theodore J.
Kim Jennifer
LandOfFree
Treating inflammatory diseases of the head and neck with... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Treating inflammatory diseases of the head and neck with..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Treating inflammatory diseases of the head and neck with... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2927274