Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1996-01-04
1998-06-23
Wilson, James O.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514822, 514885, 536 5, A61K 31705
Patent
active
057705780
DESCRIPTION:
BRIEF SUMMARY
SPECIFICATION
BACKGROUND OF THE INVENTION
The fibrinolytic system serves as a basic defense mechanism to control the deposition of fibrin both in the vascular as well as in the extra vascular systems. Proper functioning of the fibrinolytic system is necessary on the one hand to limit haemorrhagia and on the other hand thrombotic phenomena, but also to limit the formation of interstitial fibrin deposits and consequent scarring. It has been recognized that the tissue plasminogen activator (t-PA) plays an important role in the initiation of the (extrinsic) fibrinolytic cascade by the transformation of the zymogen plasminogen into the active plasmin that degrades fibrin. It has also been found that the fibrinolytic capacity of plasma is strongly dependent on the concentration of circulating t-PA. The t-PA in the plasma probably stems primarily from the vascular wall where it is localized in the endothelial cell. In addition, urokinase plasminogen activator (u-PA) plays a role in the overall fibrinolysis. It has been thought that this plasminogen activator--also at least partly--derives from the vascular wall. The main inhibitor of fibrinolysis, plasminogen activator inhibitor (PAI-1) is also synthesized by endothelial cells and data exists which shows that the relative proportion between PAs and PAI-1 is important for the fibrinolytic capacity and in turn for prevention of thrombotic events like, for example, myocardial infarction. The pharmacological regulation of t-PA, u-PA and PAI-1 synthesis is therefore useful to increase insufficient endogenous fibrinolysis.
Since both t-PA and also PAI-1 are produced by endothelial cells, the regulation of their synthesis and secretion at the level of the endothelial cell provides a rapid and direct way of influencing the fibrinolytic potential of the blood. Studies recently carried out have indicated that the production of plasminogen activators and inhibitors in various cell types is regulated by a series of factors: The synthesis of t-PA in endothelial cells is increased by a number of stimuli such as thrombin, histamine, butyrate, retinoic acid and tumor promoters as, for example, phorbol-12-myristate-13-acetate (PMA). Factors which regulate the PAI-I expression in endothelial cells include lipopolysaccharides, thrombotim, interleukin-1(IL-1), tumor necrosis factor .alpha., (TNF .alpha.), transforming growth factor .beta. (TGF .beta.), basic fibroblast growth factor (BFGF) and endothelial cell growth supplement in combination with heparin. None of the above-mentioned substances could, however, be used successfully in vivo.
Bacterial sepsis initiated by the over liberation of bacterial endotoxins (LPS) is a life threatening condition in which changes in coagulation and fibrinolysis initiated by LPS produce intervascular clotting and, in turn, organ failure. it is thought that LPS operates upon endothelial cells in which the expression of tissue factor (TF) and PAI-1 are increased.
To date there is no satisfactory direct treatment of patients which can cure intervascular clotting induced by LPS and efforts to deal with the systems triggered by LPS like, for example, hypercoagulation, are on the one hand limited to heparin and on the other by treatment of the bacterial sepsis with antibiotics. In China, the Chinese herbal drug Panax notoginseng or triterpensaponins have been used by traditional Chinese doctors to relieve pain and treat cardiovascular heart disease and stasis for thousands of years.
Indeed for example in L. Zechmeister, Progress in the Chemistry of Organic Natural Products, Vol. 46,Springer-Verlag, Vienna, N.Y., 1984,in the chapter on "Saponins of Ginseng and Related Plants", the characteristics of Panax notoginseng as a tonic, a haemostat, a coronary therapeutic and an antihaemorrhagic have been described. Also there is an indication in Chemical Abstracts 119, 85 683 as to the antihaemorrhagic effect of Panax notoginseng and in the Japanese Patent Abstracts JP Kokai No. 55-127 317,as to the antifibrinolytic effect and in JP Kokai No. 63-198 609 as
REFERENCES:
patent: 4708949 (1987-11-01), Liu
patent: 4795742 (1989-01-01), Liu
Pan et al., Chin. J. Pharmacol. Toxicol., vol. 7(2): 141-144, (1993). Abstract only.
Zhao et al., Immunopharmacology, vol. 20(3): 225-234, (1990). Abstract only.
You-Tang et al., Acta Pharmacol. Sin., vol. 7(5): 439-442, (1986). Abstract only.
Matsuda et al., Chem. Pharm. Bull., vol. 34(3): 1153-1157, (1986). Abstract only.
Kubo et al. Yakugaku Zasshi, vol. 104(7), pp. 757-762, (1984).
Planta Medica, vol. 55, No. 1, pp. 18-21, Feb. 1989.
Chem. Pharm. Bull., vol. 34, No. 5, pp. 2100-2104, May 1986.
Chem. Pharm. Bull., vol. 34, No. 3, pp. 1153-1157, Mar. 1986.
Chem. Pharm. Bull., vol. 39, No. 5, pp. 1185-1188, 1991.
Annals of Hematology, vol. 70, Supplement 1, p. A92, 1995.
Fibrinolysis, vol. 8, Supplement 1, p. 119, 1994.
Fibrinolysis, vol. 8, Supplement 1, p. 150, 1994.
Chemical Abstracts, 104:183310j 1986.
Chemical Abstracts, 119:85683y 1993.
Patent Abstracts of Japan 55-127317, 1980.
Patent Abstracts of Japan 63-198609, 1988.
Binder Bernd
Wojta Johann
Zhang Weijian
Bergi GmbH
Dubno Herbert
Lee Howard C.
Myers Jonathan
Wilson James O.
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