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
1998-03-10
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
057261830
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/SE95/00245, filed 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 psoriasis or conditions associated with psoriasis.
BACKGROUND OF THE INVENTION
Psoriasis is a common disease which affects about 2% of the population of Scandinavia.
Hereditary factors are important. If one parent has psoriasis, the risk for the child is 25% and if both parents have psoriasis there is a risk of 60-70%. Drugs thought to precipitate or worsen psoriasis include alcohol and, in some patients, .beta.-blockers and non-steroidal anti-inflammatory agents.
Psoriasis is characterised by thickened, erythematous, well-demarcated areas of skin covered by silvery scales. The extent of involvement ranges from isolated, small lesions to the whole body surface. Nails are involved in up to 50% of psoriasis patients. Because of the heterogenic nature of psoriasis, other papulosquamous dermatoses may need to be considered in the differential diagnosis. There are several clinical forms of psoriasis and it can change qualitatively from stable plaque lesions to an unstable form typified by eruptive inflammatory lesions.
Psoriatic arthritis is defined as "psoriasis (of skin or nails) associated with inflammatory arthritis (peripheral and/or spinal) and usually a negative serological test for rhematoid factor". The incidence of arthritis in the psoriatic population is about 7%. The clinical features of psoriatic arthritis are: (1) distal arthitis--an asymmetrical arthritis involving the terminalinterphalangeal joints of the hands and interphalangeal joints of the toes; there is invariably nail involvement; (2) artrophathy indistinguishable from rheumatoid arthritis, although milder; (3) a severe deforming type of arthristis (psoriatic arthritis mutilans), producing osteolysis of the hands and feet, usually associated with severe inflammatory forms of psoriasis; (4) an ankylosing spondylopathy; and (5) a mono-arthritis or oligo-arthritis.
Psoriasis is not a static disease: seasonal fluctuations, spontaneous remissions, and physical and emotional welt-being all affects the disease and hence its management. Most patients with localised, plaque-type psoriasis are able to centroll their disease at home with topical therapy with corticosteroid creams and ointments. For the more widespread forms, some form of phototherapy, either alone or combined with topical therapy, is usually needed. In resistant psoriasis, photochemotherapy or systemic therapy may be indicated.
Methotrexate is indicated only for recalcitrant psoriasis, unresponsive to topical therapy. The main side effects are acute marrow suppression and a long term risk of hepatic fibrosis and cirrhosis which is related to cumulative life time dosage and regimen employed. Retinoid is a generic name that includes naturally occuring compounds with vitamin A activity and any synthetic analogues of retinol. As with methotrexate, retonoid therapy is restricted to severe, recalcitrant psoriasis. It is especially valuable for initial treatment of the severe, inflammatory forms of the disease, that is erythrodermic or postular psoriasis, producing a more rapid response than methotrexate. Cyklosporin is effective for severe psoriasis, and providing that guidelines for treatment are observed it also seems safe when used over periods of up to a year. However, as the long term safety of cyklosporin in patients with psoriasis is still to be established it is not the drug of choice for the patient likely to be require continous treatment for many years. The main side effects are hypertension and renal impairment, both of which are reversible if guidelines for treatment are followed. In other clinical conditions, such as immunesuppression after transplantation, the incidence of lymphoma is increased in people receiving cyklosporin long term.
Quinoline-3-carboxamide compounds have been suggested as pharmaceuticals. The compounds have comp
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Gjorstrup Per
Nilsson Bo
Svedberg Agneta
Cintins Marianne M.
Jones Dwayne C.
Pharmcia & Upjohn
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