Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-04-08
1996-12-03
Goldberg, Jerome D.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61K 3147
Patent
active
055808824
DESCRIPTION:
BRIEF SUMMARY
The present invention concerns the use of Quinoline-3carboxamide compounds, in particular roquinimex (Linomide.RTM.), or a pharmaceutically and physiologically acceptable salt thereof that is therapeutically active, for the treatment of multiple sclerosis (MS).
BACKGROUND OF THE INVENTION
Multiple sclerosis (MS) is the most common acquired neurologic disease of young adults in we, stem Europe and North America. It accounts for more disability and financial loss, both in lost income and in medical care, than any other neurologic disease of this age group. There are approximately 250.000 cases of MS in the United States.
MS affects the central nervous system and involves a demyelination process i.e. the myelin sheats are lost whereas the axons are preserved. In the central nervous system (CNS), oligodendrocytes send out processes to axons that envelope them with layers of plasma membrane that are compacted and then constitute the myelin. Myelin provides the isolating material that enables rapid nerve impulse conduction. Evidently, in demyelination, this property is lost. Although the pathogenic mechanisms responsible for MS are not understood, several lines of evidence indicate that demyelination has an immunopathologic basis. The pathologic lesions, the plaques, are characterized by infiltration of immunologically active cells such as plasma cells, macrophages and activated T cells (1). The T cells present in the cerebrospinal fluid of MS patients during acute attacks have been reported to be oligoclonal as judged by their T cell receptor usage, a finding which indicate a response to a particular antigen (2). The latter suggestion is also supported by immunogenetic studies showing an association of MS with certain MHC class II alleles (3). Increased cerebrospinal fluid immunoglobulin is consistently found in MS (4), and a variety of abnormalities in T cell functions have been described (5).
The ultimate treatment of MS would be the repair of damaged CNS myelin. Although there is no indication that the goal will be achieved soon, recent advances in understanding the biology of glial cells (which manufacture and maintain myelin) suggest that such treatment may be feasible eventually. Current treatment of MS falls into three categories: treatment of acute exacerbations, modulation of progressive disease, and therapy for specific symptoms.
Corticosteroids and ACTH have been shown to be useful in shortening the mount of time required for recovery from an exacerbation of MS. The mechanism of this effect is unknown. These medications do not increase the extent of recovery, nor do they prevent subsequent exacerbations. It has been established recently that corticosteroids are as useful as ACTH for treatment of acute exacerbations. Neither medication has been shown to be beneficial in chronic administration. Use of corticosteroids should be reserved for the treatment of dear-cut neurologic signs that are disabling. For the treatment of life-threatening exacerbations, most commonly, involving brain stem compromise, methylprednisolone in large doses (1 g IV daily for three days) has been used.
Hyperbaric oxygen treatment has recently been shown in several well-controlled trials to be completely ineffective as a treatment for all forms of MS. The antiviral substance transfer factor has been shown to be ineffective in a limited trial.
Since the immune system is believed to be involved in the development of the pathogenic process in MS, the use of immunosuppressive therapy has recently received widespread attention. Cyclophosphamide, administered in a regimen sufficient to induce lymphopenia, has been demonstrated to stabilize symptoms in patients with chronic progressive MS. Unfortunately, the effect is transient and treated and control patients are indistinguishable 3 years after treatment (6). Other general immunosuppressive treatment such as total lymphoid irradiation or treatment with azathioprine has only resulted in slight effects on symptoms (7, 8). Recently, a large multicenter trial of cyclosporine A indicat
REFERENCES:
patent: 4547511 (1985-10-01), Eriksoo et al.
patent: 5310913 (1994-05-01), Gunnarsson et al.
Carlsten, H., APMIS, 97:728, 1989.
Cook, S. D., Ann. Neurol. 22:634-638, 1987.
Dhib-Jalbut, S., Annal. Allergy, 64:433-444, 1990.
Hauser, S. L., N. Eng. J. Med., 308:173-183, 1983.
Kalland, T., J. Immunol., 134:3956, 1985.
Kalland, T., Cancer Res., 46:3018, 1986.
Kalland, T., J. Immunol., 144:4472-4476, 1990.
Kappos, L., Ann. Neurol., 23:56-63, 1988.
Karussis, D. M., Autoimmunity 1992:101.
Karussis, D. M., J. Neurol., 1992, 239 (suppl 2):S96.
Karussis, D. M., Neurology 42 (suppl 3):346, 1990.
Karussis, D. M., J. Neuroimmunol., 1991; 1(suppl):159.
Larsson, E. L., Int. J. Immunopharmacol., 9:425, 1987.
Mehta, P. J., Neurol., 32:372-77, 1982.
Myrianthopoulos, N. C., Handbook of Clinical Neurology, 47:289, 1985.
Oksenberg, J. R., Nature, 345:344-347, 1990.
Patzold, U., J. Neurolog. Sci., 54:377-394, 1982.
Prineas, J. W., Koetsier, J. C. (ed.) Handbook of Clinical Neurology, pp. 213-257, Elsevier Science Publ., Amsterdam, 1985.
Tarkowski, A., Arthr. Rheum., 29:1405-1409, 1986.
Abramsky Oded
Karussis Dimitrios
Lehamann Dan
Slavin Shimon
Goldberg Jerome D.
Kabi Pharmacia AB
LandOfFree
Use of substituted quinoline carboxamide does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of substituted quinoline carboxamide, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of substituted quinoline carboxamide will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-785891