Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1989-09-19
1992-09-08
Griffin, Ronald W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 21, 536 54, 536 551, 536121, A61K 31715, A61K 3172
Patent
active
051458411
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to compounds, compositions and methods for the treatment of arthritis and allied inflammatory conditions. More particularly the invention relates to novel metallo complexes of polysulphated polysaccharides, compositions including those compounds, compositions including any two of the compounds selected from hyaluronic acid or water soluble salts thereof, corticosteroids and compounds capable of maintaining the integrity of connective tissues, particularly joint articular cartilage and methods for treating arthritis and allied inflammatory conditions using these compounds and compositions.
BACKGROUND ART
Arthritis and other related inflammatory conditions are generally debilitating, painful diseases that affect the joints of a significant portion of the human and other animal populations. As a result of the wide spread occurrence of such diseases, considerable medical effort has been directed towards producing and identifying therapies that are able to at least relieve some of attendant pain, and produce regression of the malady.
As a result of this work, many compounds have been found to be useful in the treatment of such inflammatory diseases with varying degrees of success being achieved in relieving the pain of the disease and the restoration of the affected joints to normal function.
One of the earliest compounds to be used to treat inflammatory disease, which was found to have some effect in relieving pain, was salicylic acid. Unfortunately, this compound was found to be excessively irritating to the gastrointestinal tract. Accordingly, many derivatives of salicylic acid were evaluated for anti-inflammatory activity which resulted in the identification of aspirin as an effective and relatively safe anti-inflammatory compound.
Since the discovery of aspirin, many other compounds have been produced which are claimed to be more effective than aspirin. These include such compounds as the phenylacetic acids exemplified by ibuprofen and more recently identified compounds such as naproxen and sulindac. Strong anti-inflammatory potency has been achieved with the corticosteroids (e.g. hydrocortisone, dexamethasone, prednisolone, methyl prednisolone, betamethasone, paramethasone, and triamcinolone) as their water soluble and insoluble derivatives and these are also widely prescribed.
However, all of these prior art compounds and compositions whilst displaying satisfactory analgesic anti-inflammatory properties, in that they relieve joint pain to a certain extent in most cases, any beneficial effect that they have in restoring joint function is usually only transitory.
Furthermore, prolonged therapy with these prior art compounds and compositions while providing continuing pain relief for many sufferers can lead to breakdown and failure of connective tissues, particularly articular cartilage which in fact may exacerbate the problem. Examples of this phenomenon are described by: Newman and Ling, Lancet Jul. 6, 11-14, 1985; Watson, Rheum. Rehab., 15, 26-30, 1976; McKenzie, Horsburgh, Ghosh and Taylor Ann. Rheum. Dis. 35, 487-417, 1976; Burkhardt and Ghosh, Seminars in Arthritis and Rheumatism, Suppl. 1, 17, 1-34, 1987. Corticosteroids, while still extensively used as anti-inflammatory agents for intra-articular treatment of severe arthropathies, are amongst the most potent inhibitors of connective tissue growth, repair and biosynthesis of matrix components (see Silbermann et al., Bone and Mineral 2, 87-106, 1987; Rimza, AM. J. Dis. Child. 132, 806-810, 1978; Canalis, Endocrinology, 112, 931-939, 1983; Reynolds, Exp. Cell. Res. 41, 174-189, 1966; Oikarinen, Biochem. Pharmacol, 26, 875-879, 1977, Silbermann et al., Growth, 47, 77-96, 1983, Saarni, Biochem. Pharmacol, 26, 1961-1966, 1977 Olah, and Kostenszky, Acta. Biol. Acad. Sci, Hung. 27, 129-134, 1976). Many clinical reports have appeared condemning the long term uses of these agents, reviewed by Neustadt, in "Osteoarthritix, Diagnosis and Management, Chapter 19, Eds. Moskowitz, Howell, Goldberg, Mankin, W. B. Sau
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Cullis-Hill David
Ghosh Peter
Arthropharm PTY. Limited
Carson Nancy S.
Griffin Ronald W.
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