Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ester doai
Patent
1994-10-21
1998-05-05
Weddington, Kevin E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ester doai
514458, 514474, 514560, 514725, A61K 3122, A61K 31355, A61K 3134, A61K 3120
Patent
active
057475334
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to the use of omega-3-fatty acids (hereafter called .omega.3-fatty acids) for the treatment of or for preventing the development of Disseminated Intravascular Coagulation (hereafter called DIC; for abbreviations, see the appended Abbreviation List) as well as reducing a pathological increase in pulmonary artery pressure (PAP). The preparations to be used may be in the form of emulsions for parenteral or enteral administration, or for example in the form of aerosols for inhalation or in a form for oral administration. The .omega.3-fatty adds (or salts or derivatives thereof) can originate from a marine or vegetable oil, from phospholipids, or be of syntheic origin.
BACKGROUND OF THE INVENTION
Today one of the major challenges for intensive care is to combat the secondary hypoperfusion syndromes seen after septicemia, trauma and malignancies. These syndromes include uncontrolled activation of the cascade systems (coagulation, fibrinolyses, kallikrein-kinin-, complement systems) often described as post traumatic micro embolism or disseminated intravascular coagulation (DIC). Disseminated intravascular coagulation (DIC) gives rise to a wide variety of symptoms, to some extent caused by massive disseminated microembolism. There seem to be various target organs partly due to the inducing agent or cause as well as to probably a number of unknown factors. A common situation in patients who develope DIC is pulmonary microembolism which could lead to severe problems of gas exchange, oedema and subsequent increase in pulmonary arterial pressure (PAP).
According to the literature (Medicine, Edited by E. Rubenstein and D. D. Federman published by Scientific American, New York, 1988, chapter 5:VI, Hemostasis and coagulation, p35-38) there are a plurality of circumstances that can initiate the DIC-syndrome. Such circumstances may be massive tissue damage, leading to the release of huge amounts of tissue thromboplastic materials, causing extensive activation of the extrinsic system or extensive destruction of endothelial surfaces. The circumstances can be caused by for example severe injuries and infections, tumor products, hemolytic transfusion reactions, vasculitis, heatstroke, hemangomias and certain snake bites. In all cases this leads to a massive activation of the hemostatic mechanisms, which overwhelms the inhibitor mechanisms.
The entire scheme of coagulation either initiated by the intrinsic, including the kallikrein-Factor XII, pathway or extrinsic pathways is finely tuned to culminate in a burst of thrombin activity, causing hemostatic activity at the site of the injury, which leads to deposition of cross-linked fibrin to form a hemostatic plug. Normally, the effects of intravascular coagulation are controlled or modulated by the dilutional effects of the blood flow, by antithrombines, antiplasmin and among other factors the mechanisms that down-regulate hemostasis. However, these control mechanisms can be overwhelmed and disordered by the circumstances mentioned above. This may lead to excessive release of thrombin, which results in thromboses, ischemic conditions and necrosis.
The DIC syndrome can thus lead to massive intravascular deposition of fibrin and impaired nutritive circulation leading to organ failure. This picture of DIC has for a long time dominated the concept of this common disorder. However, alternative views on this syndrome has also been brought forward. The fact that probably several other enzyme systems are involved in the syndrome has been focused on by suggestions on alternate names like "defibrination syndrome". This is discussed in the article of G. Muller-Berghaus in Seminars In Thrombosis and Hemostasis, vol. 15, No. 1, 1989, page 58-87, which is referred to for a review of the numerous conditions related to DIC.
Despite modern treatment modalities, the high mortality rate (>50%) from DIC has not decreased appreciably over the last 20 years. A great number of various therapies have been tried in order to prevent and also treat this syndrome. The tre
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Egberg Nils
Jakobsson Jan
Larsson-Backstrom Carin
Lundh Rolf
Pharmacia & Upjohn Aktiebolag
Weddington Kevin E.
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