Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-08-28
1998-09-01
Fonda, Kathleen K.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 53, 536 54, 536 551, A61K 31715, C08B 3700
Patent
active
058011625
DESCRIPTION:
BRIEF SUMMARY
This is the U.S. national stage entry under 35 U.S.C. .sctn. 371 of PCT/JP94/01643, filed Sep. 30, 1994.
TECHNICAL FIELD
This invention relates to antithrombotic agents which prevent the extension of thrombi and stimulate lysis thereof.
BACKGROUND ART
Thrombosis is a disease caused by blood coagulation in living blood vessels due to the imbalance of platelets, coagulation and fibrinolytic system which basically should maintain fluidity of blood in the blood vessels. Thrombi in coronary arteries cause myocardial infarction and those in venous vessels in the lower limbs and so forth cause deep vein thrombosis. Abnormal activation of coagulation system due to severe infectious diseases or tumors leads to thrombi in systemic capillary blood vessels and results in disseminated intravascular coagulation syndrome (hereinafter referred to DIC). The DIC caused by severe infectious diseases often complicates by multiple organ failure and very poor prognosis. Various countermeasures have been developed to treat the thrombosis which shows extremely various symptoms depending on the sites of onset. Urokinase, tissue plasminogen activator (hereinafter referred to t-PA) or heparin and so forth have been used for the treatment of myocardial infarction and deep vein thrombosis and heparin has also been applied to DIC. However, urokinase has drawbacks of low affinity to fibrin, and t-PA is expensive and has very short half-life. In addition, percutaneous transluminal coronary recanalization and reperfusion therapy by direct peripheral intravenous administration with t-PA are liable to cause recurrence of thrombosis. Heparin has problems which requires at a definite concentration or over of antithrombinIII to secure the desired effect to exert its therapeutic effect. Furthermore, these drugs cause serious adverse effect of bleeding, thus synthetic anti-protease drugs have been developed to cope with the difficulties. However, no sufficient solution of the adverse effect has been obtained and problems such as an extremely short half-life remain unsolved.
Dermatan sulfates have been reported to exert anti-coagulant activity via heparin cofactorII, but on their fibrinolytic activity, acceleration of release of t-PA by dermatan sulfates has been reported (Abbadini, M. et al., blood, 1987, 70, 1858-1860). while, no effect of dermatan sulfates on the amount of t-PA or fibrinolytic activity (Tripodi, A. el al., Thromb. res., 1991, 62, 663-672) has been reported and definite effect on fibrinolytic system is unclear.
Dermatan sulfates which have been used in various experiments or as a medicine under development are derived from intestine or skin of porcine or bovine (Pareed, J. et al., recent Advances in Blood Coagulation, 1993, 6, 169-187). No activity of dermatan sulfates derived from the other origins has been known.
DISCLOSURE OF INVENTION
The inventors of the present invention have been investigating the effect of dermatan sulfates on the fibrinolytic system and found that thrombolytic activity is enhanced by their presence in comparison to that in their absence. In addition, the inventors found that cumulated antithrombotic activity of dermatan sulfate administered in the living body composed of both anticoagulation and fibrinolytic activities is particularly significant for specific dermatan sulfates having intrinsic viscosity of 0.8 100 mL/g or over, specific detmatan sulfates derived from chicken crest, specific dermatan sulfates having a .DELTA.Di-OS at a rate of 2-7% in their constructing disaccharide, or specific dermatan sulfates having average molecular weight of 25,000-100.000 dalton determined by the method described later, and additionally particular specific dermatan sulfates having very low content of heparin or heparan sulfate among dermatan sulfates aforementioned. The present invention is accomplished by the above mentioned findings.
The present invention relates to the antithrombotic containing the effective ingredient of dermatan sulfates shown above or to combined use of dermatan sulfates with tissu
REFERENCES:
patent: 4783447 (1988-11-01), DelBono et al.
patent: 4818690 (1989-04-01), Paques
patent: 4943630 (1990-07-01), Jacquinet et al.
patent: 4973580 (1990-11-01), Mascellani et al.
patent: 5013724 (1991-05-01), Petitou et al.
patent: 5116963 (1992-05-01), Del Bono et al.
patent: 5118793 (1992-06-01), Tollefsen et al.
patent: 5164377 (1992-11-01), Van Dedem et al.
patent: 5252339 (1993-10-01), Cristofori et al.
patent: 5382570 (1995-01-01), Petitou et al.
patent: 5389618 (1995-02-01), Debrie
CRC Handbook of Chemistry and Physics, 58th edition, R. C. Weist, editor, CRC Press, Inc., West Palm Beach, FL, 1978, pp. F124-F125.
Conrad Ann. N.Y. Acad. Sci. 1989, 556, 18-28.
K. Nagasawa et al., "The Structure of Rooster-Comb Dermatan Sulfate. Characterization and Quantitative Determination of Copolymeric, Isomeric Tetra-and Hexa-Saccharides" Carbohydrate Research 131:301-314 (1984).
M. Abbadini et al., "Dermatan Sulphate Induces Plasminogen Activator Release in the Perfused Rat Hindquarters" Blood 70(6):1858-1860 (1987).
A. Tripodi et al., "Effects of Subcutaneously Administered DermatanSulfate (MF 701) on the Coagulation and Fibrinolytic Parameters of Healthy Volunteers" Thrombosis Research 62:663-672 (1991).
J. Fareed et al., "An Overview of Non-Heparin Glycosaminoglycans as Antithrombotic Agents" Recent Advances in Blood Coagulation pp. 169-187, 1993.
Arai Mikio
Kyogashima Mamoru
Miyauchi Satoshi
Onaya Junichi
Takada Akikazu
Fonda Kathleen K.
Seikagaku Kogyo Kabushiki Kaisha (Seikagaku Corporation)
LandOfFree
Dermatan sulfate compositions and antithrombotic compositions co does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Dermatan sulfate compositions and antithrombotic compositions co, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Dermatan sulfate compositions and antithrombotic compositions co will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-270391