Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1999-04-27
2000-09-26
Cintins, Marianne M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514886, 514887, A61K 3170
Patent
active
061242667
DESCRIPTION:
BRIEF SUMMARY
A SULPHOLIPID COMPOSITION AND METHODS FOR TREATING SKIN DISORDERS
The present invention refers to a new PAP-receptor antagonist, the sulpholipid SQDG, as well as to the use of SQDG for the prophylaxis or treatment of inflammatory skin diseases, especially psoriasis.
BACKGROUND OF THE INVENTION
Inflammatory skin diseases such as atopic dermatitis, urticaria and especially psoriasis still constitute a great problem for the affected patients as there are today no effective therapies.
Psoriasis is a common chronic inflammatory dermatosis with a global distribution; it has been estimated that about 1.5% of the population in the western countries can be expected to suffer from the disease during their lifetime. A number of different clinical patterns of psoriasis are acknowledged, the most common being plaque psoriasis.
Hyperproliferation, inflammation with massive infiltration of leucocytes and disturbances in cell differentiation are the typical characteristics of psoriatic skin. The number of basal cells is vastly increased which reduces the turn-over time for the epidermis from the normal 27 days to 3-4 days. The normal events of cell maturation and keratinization do not occur. This proliferation of keratinocytes occurs both in involved and non-involved psoriatic skin but is most pronounced in the plaques. The inflammatory infiltrate from psoriatic lesions has been found to consist predominantly of mononuclear T lymphocytes. There is a disturbed T cell function also in the circulating blood, which implies a possible cell-mediated immunological abnormality in psoriasis. The phagocytes that can be identified histologically in the psoriatic lesion, neutrophils in particular, suggest a role for the chemotactic inflammatory mediators in the pathology of psoriasis. Among these interleukin-1, -6 and -8, leukotriene B.sub.4 and PAF have been isolated in pathological amounts in the affected skin.
There is a number of different therapies of psoriasis of varying effectiveness, none being perfect. Among the antipsoriatic drugs of natural origin can be mentioned coal tar, dithranol, psoralens, retinoids and cyclosporin A. In addition to said more established therapies can also be mentioned the use of podophyllotoxin, a lignan which can be isolated from Podophyllum species, polyunsaturated fatty acids, such as eicosapentaenoic acid and gammalinolenic acid, and colchicine, an alkaloid from the crocus plant. The use of essential fatty acids in atopic dermatitis and psoriasis, respectively, are described by Wright, S., British Journal of Dermatology 125, 503-515, 1991.
In the traditional medicine of Honduras the name Calaguala is used for the extract of a number of closely related Polypodium species, including P. decumanum Willd., P. aureum (or P. leucatomos), P. lowei C. Chr., P. loriceum L., P. triseriale Sw., P. fraxinifolium Jacq. and P. dissimile L (Molina, personal communication, 1991). A decoction or infusion of the Calaguala plant has been used to treat a number of diseases including peptic ulcer, kidney problems, diarrhoea and arthritis or other pains in joints and tendons.
Over the last two decades several clinical trials have been performed on calaguala in the treatment of psoriasis, as well as atopic dermatitis (Vargas Gonzales, J. P., et al., Acta Pediatric. Esp. 46(1), 556-561, 1988) and vitiligo (Gonzales, S., et al., J. Invest. Derm. 102(4), 651, 1994).
Platelet activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a phospholipid derived mediator with a diversity of biological effects. PAF is released from various cell types, including platelets, neutrophils, monocytes and endothelial cells. In addition, several cell types, including neutrophils, are known to express specific PAF receptors on their cell membrane. In vitro PAF exhibits effects, including aggregation and degranulation of leukocytes and inhibition of lymphocyte proliferation. In vivo effects include hypotension, acute renal failure and increase in vascular permeability. PAF is thought to be associated with a number of pa
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patent: 5620962 (1997-04-01), Winget
Vasange, et al., "A Sulphonoglycolipid from the Fern Polypodium decumanum and its Effect on the Platelet Activating-factor Receptor in Human Neutrophils," J. Pharm. Pharmacol., 49, 562-566 (1997).
Morimoto, et al., "Studies on Glycolipids. VII. .sup.1) Isolation of Two New Sulfoquinovosyl Diacylglycerols from the Green Alga Chlorella vulgaris," Chem. Pharm. Bull. 41(9) 1545-1548 (1993).
Gustafson, et al., "AIDS-Antiviral Sulfolipids From Cyanobacteria (Blue-Green Algae)," Journal of the National Cancer Institute, 81(16) 1254-1258 (1989).
Bohlin Lars
Rolfsen Wenche
Vasange Mervi
Cintins Marianne M.
Kim Vickie
Scotia Lipid Teknik AB
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