Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-10-29
1998-03-17
Cintins, Marianne M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514311, A61K 3147
Patent
active
057287139
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/SE95/00244 filed on Mar. 8, 1995.
The present invention concerns the use of quinoline-3-carboxamide compounds, in particular roquinimex (Linomide.RTM.), or a pharmaceutically acceptable salt thereof for treating inflammatory bowel disease (IBD) including idiopathic ulcerative colitis (UC) and Crohn's disease.
BACKGROUND OF THE INVENTION
Inflammatory bowel disease (IBD) refers to both idiopathic ulcerative colitis (UC) and Crohn's disease. These are important chronic medical disorders of unknown etiology, characterized by symptoms of inflammation of the bowel with systemic response and also extraintestinal manifestations.
The cause of IBD is not known. The marked difference in incidence in ethnic groups and the tendency of IBD to cluster in families have suggested genetic or other host factors, but no consistent genetic markers have been found. No infectious agent has been consistently isolated. Emotional factors are probably not etiologic but they may exacerbate symptoms. The extraintestinal manifestations, the reported presence of antibodies to colonic epithelial cells and of cytotoxic T-cells and the clinical and histological response to immunosuppressive agents have suggested an immunological basis for the intestinal injury.
The incidence of UC in Scandinavia is 5 to 8 cases/100.000 inhabitants. The incidence of Crohn's disease is increasing but still a bit lower than in UC.
UC is confined to colon and rectum only. The cardinal symptoms of acute UC are diarrhea, rectal bleeding, fever, weight loss and abdominal pain. The disease can be mild but is also associated with complications such as toxic dilations of the colon and carcinoma of the colon. In Crohn's disease, the small intestine and the colon are most often affected, but any part of the gastrointestinal tract may be involved. The onset of symptoms are more subtle than in UC. The intestinal manifestations can for example be abdominal pain, diarrhea, fissures, fistulas, perirectal abscesses. Extra-intestinal manifestations in common for IBD can for example be nutrional abnormalities, anemia, diseases of the skin (erythema nodosum), arthritis (anchylosing spondylitis) and hepatic and renal abnormalities.
This formula is a collective formula for the tautomeric structures II-IV. ##STR2## In formula I-IV: (a) - - - represents that there are two conjugated double bonds between the atoms comprised by the dashed line (only formula I). NH.sup.9 group that possibly is substituted, said X.sub.1 and X.sub.2 being bound by a single bond to the ring when attached to H.sup.7 or H.sup.8 and by a double bond when not bound to H.sup.7 or H.sup.8. present when at least one of X.sub.1 and X.sub.2 is the NH.sup.9 group. selected among X.sub.1, X.sub.2 and the nitrogen atom in the quinoline ring said X.sub.1 and X.sub.2 being bound by a single bond to the ring when attached to H.sup.7 or H.sup.8 and by a double bond when not bound to H.sup.7 or H.sup.8.
The substituents that are to replace H.sup.1-9 may, according to the prior art, comprise any substituent that gives compounds that can be isolated.
The medical treatment of both UC and Crohn's disease consists mainly of sulfasalazine and corticosteroids. Mild to moderate acute UC may respond to supportive measures supplemented by sulfasalazine alone. Sulfasalazine is split by bacterial action in the colon to yield sulfapyridine and 5-aminosalicylate, the latter considered to be active agent through its local inhibition of prostaglandine and leukotriene synthesis. If this regimen is insufficient, it can be supplemented by corticosteroid therapy, given either as oral prednisone or as hydrocortisone administered as a bedtime enema. Acute severe UC may lead to toxic megacolon, a medical emergency requiring systemic corticosteroids in large doses, coverage by broad spectrum antibiotics, and in some cases emergency colectomy. In Crohn's disease the medical treatment is similar to that for UC, with sulfasalazine and corticosteroids being the main agents used beyond supportive and dietary meas
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Gjorstrup Per
Nilsson Bo
Svedberg Agneta
Cintins Marianne M.
Jones Dwayne C.
Pharmacia & Upjohn
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